List of IRIS Substances Search IRIS by Keyword

IRIS Summaries/Toxicological Reviews Entire IRIS Website

Category (section) Status Last Revised You are here: EPA Home Research Environmental Assessment IRIS IRIS Summaries

view QuickView

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. Supp orting 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 Assessmen t (II.) on-line 03/01/1991 

### _I. Chronic Health Hazard Assess ments 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 Asse ssment 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 extrap olation procedure and is presente d as the risk per (mg/kg)/day. The unit risk is the quantitative estimate in terms of either risk per ug/L dr inking water or risk per ug/cu.m air breathed. The third form in which ri sk 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 (E PA/600/8-87/045) and in the IRIS Background Document. IRIS summaries developed since the pu blication 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). User s 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-Evid ence Characterization Classification — B2; probable human carcinogen Basis — Based upon the observat ion of pulmonary carcinomas and malignant tumors at various sites in rats administered nickel carbonyl by in halation 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 fr om a study of workers ata 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 carb onyl; 64 rats were exposed to 0.03 mg/L three times weekly for 1 year, 32 ratswere exposed to 0.06 mg/L th ree times weekly for 1 year, and 

### http://www.epa.gov/iris/subst/0274.htm80 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 mo re years, four were reported to have tumors. One animal with re peated exposure to 0.03 mg/L had a squamous-cell carcinoma; one animal with repeated exposu re 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 ad enocarcinomatous pattern, and the other had two small papillary bronchial adenomas. No pulmonary tumors were seen in the three surviving controls. Sunderman and Donnelly (1965) treate d male Wistar rats in six grou ps (three were controls). The exposure groups consisted of th e following: (a) 285 animals expose d 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 th eir lifetimes. In the chronic and acute nickel carbonyl exposure groups, three animals of the 80 surviving the 2-year exposure and/or observation pe riod showed pulmonary carcinom as 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 prod uced 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 radi oactive nickel ca rbonyl, nickel was bound to the liver and kidney DNA.

_II.B. Quantitative Estimate of Carcin ogenic Risk from Oral Exposure The low survival rate for both control and trea ted animals in the stud ies of Sunderman and coworkers and the intravenous rout e of exposure in the study byLau et al. (1972) preclude a quantitative risk estimate.

_II.C. Quantitative Estimate of Carcinog enic Risk from Inhalation Exposure None.

_II.D. EPA Documentation, Review, and Contacts (C arcinogenicity Assessment) __II.D.1. EPA Documentation Source Document — U.S. EPA, 1986 The 1986 Health Assessment Document has rece ived both Agency and external review. __II.D.2. EPA Review (Car cinogenicity Assessment) Agency Work Group Review — 04/01/1987 

### http://www.epa.gov/iris/subst/0274.htmVerification Date — 04/01/1987 Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent to xicology literature pertinent to th e cancer assessment for Nickel carbonyl conducted in November 2001 did not iden tify 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 co ncerning 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. CarcinogenicityAssessment References Hui, G. and F.W. Sunderman. 1 980. Effects of nickel compounds on incorporation of thymidine - 3H into DNA in rat liver and kid ney. Carcinogen esis. 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. Re spiratory cancer mortality of Welsh nickel refinery workers. Nickel in the Human Environment: Proceedings of a Joint Symposium, March 1983. Internat ional Agency for Research of Cancer, Lyon, France. IARC Scientific Pub. No. 53. p. 36-46. Sunderman, F.W. and A.J. Donne lly. 1965. Studies of nickel carcinogenesis metastasizing pulmonary tumors in rats induce d by the inhalation of nickel carbonyl. Am. J. Pathol. 46: 1027. 

### http://www.epa.gov/iris/subst/0274.htmDate Section Description

IRIS Home Chronic HealthHazards for NonCarcinogenic Effects Sunderman, F.W., A.J. Donnelly, B. West and J.F. Kincaid. 1959. Nickel poisoning. IX. Carcinogenesis in rats exposed to nick el carbonyl. Arch. Ind. Health. 20: 36. U.S. EPA. 1986. Health As sessment Document for Nickel and Ni ckel Compounds. Prepared by the Office of Health and Environm ent Assessment, Environmental Cr iteria 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-Leve l Literature Review Findin gs 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.htmReference 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