Safe use of nickel in the workplace Module 1: toxicology and hazard classification of nickel substances

KNOWLEDGE

FOR A BRIGHTER

FUTURE

Safe use of nickel in the workplace Module 1: toxicology and hazard classification of nickel substances

A GUIDE FOR HEALTH

MAINTENANCE OF WORKERS

EXPOSED TO NICKEL, ITS

COMPOUNDS AND ALLOYS

FOURTH EDITION

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Safe use of nickel in the workplace Module 1: toxicology and hazard classification of nickel substances

A GUIDE FOR HEALTH MAINTENANCE OF WORKERS EXPOSED TO NICKEL, ITS COMPOUNDS AND ALLOYS

FOURTH EDITION

Material presented in the handbook has been prepared for the general information of the reader and should not be used or relied on for specific applications without first securing competent advice.

The Nickel Institute, their members, staff and consultants do not represent or warrant its suitability for any general or specific use and assume no liability or responsibility of any kind in connection with the information herein.

Nickel Institute

[e-mail]

www.nickelinstitute.org

Safe use of nickel in the workplace Module 1: toxicology and hazard classification of nickel substances

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Contents

1. About this guide . . . . . . . . . . . . . . 5 4.2.2 Dermal exposure: nickel alloys . . . . . . . . .24

1.1 Summary . . . . . . . . . . . . . . . . . . 6 4.3 Soluble nickel . . . . . . . . . . . . . . . . 25

1. Production and use . . . . . . . . . . . . . . 6 4.3.1 Inhalation exposure: soluble nickel . . . . . . .25
2. Sources of exposure . . . . . . . . . . . . . . 6 4.3.2 Dermal exposure: soluble nickel . . . . . . . .27
3. Pharmacokinetics of nickel . . . . . . . . . . . 7 4.3.3 Other exposures: soluble nickel . . . . . . . . 27

1.5	Summary of the toxicity of nickel substances .	.	. 8	4.4	Oxidic nickel . . . . . . . . . . . . . . . . .29
1.5.1	Summary of the toxicity of metallic nickel . . .	.	8	4.4.1	Inhalation exposure: oxidic nickel . . .	. . . . 30
1.5.2	Summary of nickel metal alloys . . . . . . .	.	. 9	4.5	Sulfidic nickel . . . . . . . . . . . . .	. .	.	32
1.5.3	Summary of the toxicity of soluble nickel . . .	.	. 9	4.5.1	Inhalation exposure: sulfidic nickel . . .		. . . .33
1.5.4	Summary of the toxicity of oxidic nickel . . . .	.10	4.6	Nickel carbonyl . . . . . . . . . . .	.	. .	.	34

1.5.5 Summary of the toxicity of sulfidic nickel . . . . 11 4.6.1 Inhalation exposure: nickel carbonyl . . . . . . 34

1.5.6	Summary of the toxicity of nickel carbonyl . .	.		.11	5.	Hazard classifications . . . . . . . .	. .	. 35
1.5.7	Summary of hazard classifications . . . . .	.	.	11
5.1	Acute toxicity . . . . . . . . . . . . . . . . 35
2.	Production and use . . . . . . . . . .	.	. 13	5.2	Skin corrosion/irritation & serious eye
2.1	Nickel-producing industries . . . . . . . . . .13		damage/eye irritation . . . . . . . . . . . . .36
2.2	Nickel-using industries . . . . . . . . . .	.	.	15	5.3	Respiratory or skin sensitisation . . . .	. . . .36
3.	Pharmacokinetics of nickel compounds .	.	. 15	5.4	Germ cell mutagenicity . . . . . . . .	. . .	.37
5.5	Carcinogenicity . . . . . . . . . . . .	. .	. 37
3.1	Intake . . . . . . . . . . . . . . . . . . .		.16
	5.6	Reproductive toxicity . . . . . . . . .	. . .	.37
3.2	Absorption . . . . . . . . . . . . . . . .	.	16
5.7	Specific target organ toxicity . . . . . .	. . .	.38
3.2.1	Respiratory tract deposition, absorption and
	retention . . . . . . . . . . . . . . . .	.	.	16	6.	References . . . . . . . . . . . .	. . .	39

1. Dermal absorption . . . . . . . . . . . . . .17
2. Gastrointestinal absorption . . . . . . . . . .18

1. Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18
2. Excretion . . . . . . . . . . . . . . . . . . 19
3. Factors affecting metabolism . . . . . . . . . 19

4. Toxicity of metallic nickel and

nickel compounds . . . . . . . . . . . . 20

1. Metallic nickel . . . . . . . . . . . . . . . . 20 4.1.1 Inhalation exposure: metallic nickel . . . . . . .20 4.1.2 Dermal exposure: metallic nickel . . . . . . . .23
2. Nickel alloys . . . . . . . . . . . . . . . . .23 4.2.1 Inhalation exposure: nickel alloys . . . . . . . 23

Nickel Institute

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Safe use of nickel in the workplace Module 1: toxicology and hazard classification of nickel substances

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A guide for health maintenance of workers exposed to nickel, its compounds and alloys

1. ABOUT THIS GUIDE

Investigation into the toxicological effects of nickel salts on animals was first reported in 1826. Since that time, numerous reports and papers have been generated on the human health and environmental effects of nickel. The reported effects of nickel and its compounds on humans are wide ranging, comprising effects that are both beneficial - the probable essentiality of nickel in humans - as well as harmful

• skin allergy and, in certain circumstances, respiratory cancer. Although nickel has been studied extensively, there is still much to be learned about this ubiquitous metal. Given the role of nickel to industrialised societies, it is important to have a guide for evaluating workplace exposures and health risks in order to promote safe handling of nickel materials. The first edition of this Guide was prepared in 1993 by
  the Nickel Producers Environmental Research Association (NiPERA) in collaboration with the Nickel Development Institute (now the Nickel Institute). The second edition of the Guide was published in 1997. Subsequent to that printed edition, the Guide was published online and was revised
  in 2002, 2004 and 2008. The current version of the Guide, updated in 2021, is the fourth edition and it reflects the evolving nature of the knowledge about the health concerns associated with working with nickel, nickel compounds and alloys. The fourth edition is divided into two modules; Module 1, on the Toxicology and Hazard Classification of Nickel Substances, was updated in 2021 and Module 2, on the Exposure of Workers to Nickel Substances and Health Assessment, is to be updated in 2022. These two modules will allow independent updates in the future with new information on nickel toxicology or worker exposures and health assessment.

This Guide has been written for those individuals who are responsible for the health maintenance of workers exposed to nickel, its compounds, and alloys. As such, it is directed to a variety of individuals including operational managers, business managers, industrial hygienists, occupational health nurses, physicians, joint occupational health and safety committees, and other health professionals. Its purpose is not only to educate the reader about the potential hazards associated with exposure to various forms of nickel but also to instruct the reader in the safe handling of nickel-containing substances in the workplace. Like all scientific documents, the information contained within this Guide constitutes a "snapshot" and is subject to change as knowledge is gained about nickel. Further updates are necessary.

Certain conventions have been followed in preparing this Guide. Since it mainly addresses the health effects associated with occupational exposure to nickel and nickel- containing substances, evaluations are based predominantly on epidemiological and clinical studies, complemented by animal studies. Most evaluations are qualitative and reflect the overall weight-of-evidence reported from studies of nickel workers. Discussions of the health effects related to working with nickel compounds focus on specific forms of nickel when feasible. Because they are not present in most work environments, organometallic nickel compounds, with the exception of a brief discussion on the acute toxicity of nickel carbonyl, are not discussed within this Guide. Finally, unless noted otherwise, statements regarding the "solubility" of nickel compounds are made with respect to their solubility in biological fluids as opposed to water.

The Guide Module 1 has been organised into a summary followed by sections on production, pharmacokinetics, toxicology, and hazard classification.

Nickel Institute