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Reference Dose for Chronic Oral Exposure (RfD) 

0274

Nickel carbonyl; CASRN 13463-39-3

Human health assessment information on a chemical substance is included in the IRIS database 

only after a comprehensive review of toxicity data, as outlined in the IRIS assessment 

development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II 

(Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached 

during the assessment development process. Supporting information and explanations of the 

methods used to derive the values given in IRIS are provided in the guidance documents located 

on the IRIS website. 

STATUS OF DATA FOR Nickel carbonyl

File First On-Line 09/30/1987

Oral RfD Assessment (I.A.) no data

Inhalation RfC Assessment (I.B.) no data

Carcinogenicity Assessment (II.) on-line 03/01/1991 

_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects

_I.A. Reference Dose for Chronic Oral Exposure (RfD)

Substance Name — Nickel carbonyl 

CASRN — 13463-39-3

Not available at this time.

Integrated Risk Information System

http://www.epa.gov/iris/subst/0274.htm

Last updated on Thursday, August 09, 2012

http://www.epa.gov/iris/subst/0274.htm
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — Nickel carbonyl

CASRN — 13463-39-3

Not available at this time.

_II. Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Nickel carbonyl

CASRN — 13463-39-3

Last Revised — 03/01/1991

Section II provides information on three aspects of the carcinogenic assessment for the substance 

in question; the weight-of-evidence judgment of the likelihood that the substance is a human 

carcinogen, and quantitative estimates of risk from oral exposure and from inhalation exposure. 

The quantitative risk estimates are presented in three ways. The slope factor is the result of 

application of a low-dose extrapolation procedure and is presented as the risk per (mg/kg)/day. 

The unit risk is the quantitative estimate in terms of either risk per ug/L drinking water or risk per 

ug/cu.m air breathed. The third form in which risk is presented is a drinking water or air 

concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1 in 1,000,000. The rationale 

and methods used to develop the carcinogenicity information in IRIS are described in The Risk 

Assessment Guidelines of 1986 (EPA/600/8-87/045) and in the IRIS Background Document. IRIS 

summaries developed since the publication of EPA's more recent Proposed Guidelines for 

Carcinogen Risk Assessment also utilize those Guidelines where indicated (Federal Register 61

(79):17960-18011, April 23, 1996). Users are referred to Section I of this IRIS file for 

information on long-term toxic effects other than carcinogenicity. 

_II.A. Evidence for Human Carcinogenicity

__II.A.1. Weight-of-Evidence Characterization

Classification — B2; probable human carcinogen 

Basis — Based upon the observation of pulmonary carcinomas and malignant tumors at various 

sites in rats administered nickel carbonyl by inhalation and intravenous injection, respectively. 

Nickel administered as nickel carbonyl binds to DNA. 

__II.A.2. Human Carcinogenicity Data

Inadequate. Nickel carbonyl was the first nickel compound suspected of causing cancer in humans 

in a detailed analysis of epidemiologic data from a study of workers at a sulfide nickel matte 

refinery at Clydach, Wales. No excess risk of cancer, however, was reported in the workers in the 

reduction area where nickel carbonyl exposure was present (Peto et al., 1984). 

__II.A.3. Animal Carcinogenicity Data

Sufficient. Nickel carbonyl administered by inhalation has been found to be carcinogenic in 

animals in the lung (Sunderman et al., 1959, Sunderman and Donnelly, 1965). Sunderman et al. 

(1959) exposed male Wistar rats to nickel carbonyl; 64 rats were exposed to 0.03 mg/L three 

times weekly for 1 year, 32 rats were exposed to 0.06 mg/L three times weekly for 1 year, and 

http://www.epa.gov/iris/subst/0274.htm
80 rats were exposed once to 0.25 mg/L. In each case, exposure was for 30-minute periods. Of 

the nine animals exposed to nickel carbonyl and surviving 2 or more years, four were reported to 

have tumors. One animal with repeated exposure to 0.03 mg/L had a squamous-cell carcinoma; 

one animal with repeated exposure to 0.06 mg/L showed masses of clear-cell carcinoma having 

an adenocarcinomatous pattern; and of two animals from a single heavy exposure, one exhibited 

masses of clear-cell carcinoma having the adenocarcinomatous pattern, and the other had two 

small papillary bronchial adenomas. No pulmonary tumors were seen in the three surviving 

controls. 

Sunderman and Donnelly (1965) treated male Wistar rats in six groups (three were controls). The 

exposure groups consisted of the following: (a) 285 animals exposed to 0.6 mg/L of carbonyl for 

30 minutes and followed for their lifetimes; (b) 60 animals exposed as in (a), but receiving an 

injection of "dithiocarb" nickel chelate 15 minutes after exposure; and (c) 64 animals exposed for 

30 minutes three times weekly to 0.03 mg/L carbonyl for the remainder of their lifetimes. In the 

chronic and acute nickel carbonyl exposure groups, three animals of the 80 surviving the 2-year 

exposure and/or observation period showed pulmonary carcinomas and metastases: one with 

pulmonary adenocarcinoma, one with anaplastic carcinoma, and one with adenocarcinoma. No 

pulmonary neoplasms were observed in any of the 44 surviving controls. 

Intravenous injection of Sprague-Dawley rats produced malignant tumors at various sites (Lau et 

al., 1972). 

__II.A.4. Supporting Data for Carcinogenicity 

Hui and Sunderman (1980) found that after exposure of rats to radioactive nickel carbonyl, nickel 

was bound to the liver and kidney DNA. 

_II.B. Quantitative Estimate of Carcinogenic Risk from Oral Exposure

The low survival rate for both control and treated animals in the studies of Sunderman and 

coworkers and the intravenous route of exposure in the study by Lau et al. (1972) preclude a 

quantitative risk estimate. 

_II.C. Quantitative Estimate of Carcinogenic Risk from Inhalation Exposure

None.

_II.D. EPA Documentation, Review, and Contacts (Carcinogenicity Assessment)

__II.D.1. EPA Documentation

Source Document — U.S. EPA, 1986 

The 1986 Health Assessment Document has received both Agency and external review. 

__II.D.2. EPA Review (Carcinogenicity Assessment)

Agency Work Group Review — 04/01/1987 

http://www.epa.gov/iris/subst/0274.htm
Verification Date — 04/01/1987 

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

contractor of the more recent toxicology literature pertinent to the cancer assessment for Nickel 

carbonyl conducted in November 2001 did not identify any critical new studies. IRIS users who 

know of important new studies may provide that information to the IRIS Hotline at 

hotline.iris@epa.gov or (202)566-1676.

__II.D.3. EPA Contacts (Carcinogenicity Assessment)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, 

at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address). 

_III. [reserved]

_IV. [reserved] 

_V. [reserved]

_VI. Bibliography 

Substance Name — Nickel carbonyl

CASRN — 13463-39-3

Last Revised — 12/01/1989

_VI.A. Oral RfD References

None

_VI.B. Inhalation RfC References

None

_VI.C. Carcinogenicity Assessment References

Hui, G. and F.W. Sunderman. 1980. Effects of nickel compounds on incorporation of thymidine - 

3H into DNA in rat liver and kidney. Carcinogenesis. 1: 297-304. 

Lau, T.J., R.L. Hackett and F.W. Sunderman. 1972. The carcinogenicity of intravenous nickel 

carbonyl in rats. Cancer Res. 32: 2253. 

Peto, J., H. Cuckle, R. Doll, C. Hermon and L.G. Morgan. 1984. Respiratory cancer mortality of 

Welsh nickel refinery workers. Nickel in the Human Environment: Proceedings of a Joint 

Symposium, March 1983. International Agency for Research of Cancer, Lyon, France. IARC 

Scientific Pub. No. 53. p. 36-46. 

Sunderman, F.W. and A.J. Donnelly. 1965. Studies of nickel carcinogenesis metastasizing 

pulmonary tumors in rats induced by the inhalation of nickel carbonyl. Am. J. Pathol. 46: 1027. 

http://www.epa.gov/iris/subst/0274.htm
Date Section Description

IRIS Home

Chronic Health 

Hazards for NonCarcinogenic Effects

Sunderman, F.W., A.J. Donnelly, B. West and J.F. Kincaid. 1959. Nickel poisoning. IX. 

Carcinogenesis in rats exposed to nickel carbonyl. Arch. Ind. Health. 20: 36. 

U.S. EPA. 1986. Health Assessment Document for Nickel and Nickel Compounds. Prepared by the 

Office of Health and Environment Assessment, Environmental Criteria and Assessment Office, 

Research Triangle Park, NC. EPA/600/8- 83/012FF. 

_VII. Revision History

Substance Name — Nickel carbonyl

CASRN — 13463-39-3

12/01/1989 VI. Bibliography on-line

06/01/1990 IV.A.1. Area code for EPA contact corrected

03/01/1991 II.A.1. Text edited

01/01/1992 IV. Regulatory actions updated

04/01/1992 IV.A.1. CAA regulatory action withdrawn

04/01/1997 III., IV., 

V.

Drinking Water Health Advisories, EPA Regulatory Actions, and 

Supplementary Data were removed from IRIS on or before April 1997. 

IRIS users were directed to the appropriate EPA Program Offices for this 

information.

12/03/2002 II.D.2. Screening-Level Literature Review Findings message has been added.

_VIII. Synonyms

Substance Name — Nickel carbonyl

CASRN — 13463-39-3

Last Revised — 09/30/1987

• 13463-39-3

• NICHEL TETRACARBONILE

• Nickel carbonyl

• NICKEL CARBONYLE

• NICKEL TETRACARBONYL

• NICKEL TETRACARBONYLE

• NIKKELTETRACARBONYL

• RCRA WASTE NUMBER P073

• UN 1259

http://www.epa.gov/iris/subst/0274.htm
Reference Dose for 

Chronic Oral 

Exposure (RfD)

• Oral RfD 

Summary 

• Principal and 

Supporting 

Studies

• Uncertainty and 

Modifying Factors

• Additional 

Studies/Comments

• Confidence in the 

Oral RfD

• EPA 

Documentation 

and Review

Reference 

Concentration for 

Chronic Inhalation 

Exposure (RfC)

• Inhalation RfC 

Summary

• Principal and 

Supporting 

Studies

• Uncertainty and 

Modifying Factors

• Additional 

Studies/Comments

• Confidence in the 

Inhalation RfC

• EPA 

Documentation 

and Review

Carcinogenicity 

Assessment for 

Lifetime Exposure

Evidence for Human 

Carcinogenicity

• Weight-ofEvidence 

Characterization

• Human 

Carcinogenicity 

Data

• Animal 

Carcinogenicity 

Data

• Supporting Data 

for 

Carcinogenicity

Quantitative 

Estimate of 

Carcinogenic Risk 

from Oral Exposure

• Summary of Risk 

Estimates

• Dose-Response 

Data

http://www.epa.gov/iris/subst/0274.htm
• Additional 

Comments

• Discussion of 

Confidence

Quantitative 

Estimate of 

Carcinogenic Risk 

from Inhalation 

Exposure

• Summary of Risk 

Estimates

• Dose-Response 

Data

• Additional 

Comments

• Discussion of 

Confidence

• EPA 

Documentation, 

Review and, 

Contacts

Bibliography

Revision History

Synonyms

http://www.epa.gov/iris/subst/0274.htm