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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo
Remarks:
Type of genotoxicity: other: review of published studies
Type of information:
other: review
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: review

Data source

Reference
Reference Type:
other: review of genoxicity studies
Title:
Review of in vivo genotoxicity of hexavalent chromium
Year:
2010

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
review of published studies
GLP compliance:
no
Type of assay:
other: review of published studies

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
review of published studies

Test animals

Species:
other: review of published studies
Details on test animals and environmental conditions:
review of published studies

Administration / exposure

Route of administration:
other: review of published studies
Vehicle:
review of published studies

Results and discussion

Test results
Sex:
not specified
Genotoxicity:
positive

Any other information on results incl. tables

Table1. Genotoxicity of hexavalent chromiumin vivo

Species

(test system)

End point

Re-sults

Reference

Compound

Drosophila melanogaster

Gene mutation

+

(Rasmuson 1985;Zimmering, Mason et al. 1985;Rodriguez-Arnaiz and Martinez 1986)

K-dichromate, Na-dichromate, Cr- trioxide Ca-chromate

D. melanogaster

Gene mutation

+

(Kaya, Creus et al. 2002)

K-dichromate

D. melanogaster

Gene mutation

+

(Amrani, Rizki et al. 1999)

K-chromate, K-dichromate

Human lymphocytes

Chromosomal aberrations

+

(Sarto, Cominato et al. 1982;Koshi, Yagami et al. 1984)

Stainless steel, welding fumes, Cr- trioxide

Human lymphocytes

Chromosomal aberrations

(Husgafvel-Pursiainen, Kalliomaki et al. 1982)

Stainless steel, welding fumes

Human lymphocytes

Sister chromatid exchanges

+

(Sarto, Cominato et al. 1982;Stella, Montaldi et al. 1982;Koshi, Yagami et al. 1984;Lai, Kuo et al. 1998)

Cr- plating, stainless steel, welding fumes, Cr- trioxide

Human lymphocytes

DNA strand breaks, hydroxylation of deoxyquanosine

(Gao, Levy et al. 1994)

Production of bichromate

Human lymphocytes

Sister chromatid exchanges

-

(Nagaya, Ishikawa et al. 1991)

Cr- plating

Human lymphocytes

Sister chromatid exchanges, DNA strand breaks

+

(Werfel, Langen et al. 1998)

Welding fumes

Human peripheral lymphocytes

Micronuclei

+

(Vaglenov, Nosko et al. 1999)

Cr- electroplating

Human peripheral lymphocytes

Micronuclei

+

(Benova, Hadjidekova et al. 2002)

Cr- plating

Human buccal mucosa

Micronuclei

+

(Benova, Hadjidekova et al. 2002)

Cr- plating

Human peripheral lymphocytes

Chromosome aberrations, sister chromatid exchanges

 

(Benova, Hadjidekova et al. 2002)

Cr- plating

Human peripheral lymphocytes

DNA strand breaks

+

(Gambelunghe, Piccinini et al. 2003)

Cr- plating

Human buccal mucosa

Chromosome aberrations, sister chromatid exchanges

+

(Benova, Hadjidekova et al. 2002)

Cr- plating

Human whole blood cells

Sister chromatid exchanges

+

(Wu, Wu et al. 2001)

Cr- electroplating

New polychromatic erythrocytes

Micronuclei

+

(Le Curieux, Marzin et al. 1992)

K-chromate

Rat lung (intratracheal exposure)

DNA alterations

+

(Izzotti, Balansky et al. 1998)

Na-dichromate

Rat lung (intratracheal exposure)

DNA alterations

-

(Izzotti, Balansky et al. 1998)

Na-dichromate

Rat liver (oral exposure)

DNA-protein crosslinks

 

(Coogan, Motz et al. 1991)

K-chromate

Rat liver and kidney nuclei (intraperitoneal exposure)

DNA-protein crosslinks

 

(Cupo and Wetterhahn 1985)

Cr- oxide

Rat liver, kidney, and lung nuclei (intraperitoneal exposure)

DNA-protein crosslinks

 

(Tsapakos, Hampton et al. 1983)

Na-dichromate

Rat hepatocytes (oral exposure)

Unscheduled DNA synthesis

 

(Mirsalis, Hamilton et al. 1996)

K-chromate

Mouse erythrocytes (oral exposure)

Micronuclei

-

(Shindo, Toyoda et al. 1989)

K-chromate

Mouse (B6C3F1, BALB/c) erythrocytes (oral exposure)

Micronuclei

-

(NTP 2007)

Na-dichromate dihydrate

Mouse (am3-C57BL/6) erythrocytes (oral exposure)

Micronuclei

+

(NTP 2007)

Na-dichromate dihydrate

Mouse (transplacental exposure)

DNA deletions

+

(Kirpnick-Sobol, Reliene et al. 2006)

K-dichromate

Mouse (BDF1) bone marrow cells (drinking water exposure)

Micronuclei

 

(De Flora, Iltcheva et al. 2006)

K-dichromate

Mouse (BDF1) peripheral blood cells(drinking water exposure)

Micronuclei

 

(De Flora, Iltcheva et al. 2006)

K-dichromate

Mouse (BDF1) bone marrow cells(drinking water exposure)

Micronuclei

 

(De Flora, Iltcheva et al. 2006)

Na-dichromate

Mouse (BDF1) peripheral blood cells(drinking water exposure)

Micronuclei

 

(De Flora, Iltcheva et al. 2006)

Na-dichromate dihydrate

Mouse (BDF1) bone marrow cells (gavage exposure)

Micronuclei

 

(De Flora, Iltcheva et al. 2006)

K-dichromate

Mouse (Swiss) fetal peripheral blood cells(transplacental exposure from intraperitoneal injection)

Micronuclei

 

(De Flora, Iltcheva et al. 2006)

K-dichromate

Mouse leukocytes

DNA damage

+

(Devi, Rozati et al. 2001)

K-dichromate

Mouse erythrocytes (intraperitoneal exposure)

Micronuclei

-

(Shindo, Toyoda et al. 1989)

K-chromate

Mouse erythrocytes (intraperitoneal exposure)

Micronuclei

+

 (Wild 1978;Itoh and Shimada 1997)

K-chromate

Mouse erythrocytes (intraperitoneal exposure)

Micronuclei

+

 (Itoh and Shimada 1997)

K-chromate

Mouse peripheral lymphocytes

DNA damage

+

(Wang, Xing et al. 2006)

K-chromate

Mouse bone marrow cells (oral exposure)

Micronuclei

-

(Mirsalis, Hamilton et al. 1996)

K-chromate

Mouse bone marrow cells (gavage)

Chromosomal aberrations

+

(Chorvatoviĉova and Ginter 1993)

Cr- trioxide

Mouse bone marrow cells (intraperitoneal exposed)

Cell mutation

+

(Chorvatoviĉova, Kováĉikova et al. 1989)

K-dichromate

Mouse hepatocytes (intraperitoneal exposed)

Cell mutation

+

(Chorvatoviĉova, Kováĉikova et al. 1989;Itoh and Shimada 1997)

K-dichromate

Mouse bone marrow cells (intraperitoneal exposed

Micronuclei

+

(Chorvatoviĉova, Kováĉikova et al. 1989;Chorvatoviĉova and Ginter 1993;Wroñska-Nofer, Wisniewska-Knypl et al. 1999)

K-dichromate

Mouse (intraperitoneal exposure)

Dominant lethality

+

(Paschin, Zacepilova et al. 1982)

K-dichromate

Mouse liver and kidney cells (intraperitoneal exposure)

Single strand breaks

+

(Ueno, Kashimoto et al. 2001)

K-dichromate

Mouse spleen, lung, and brain cells (intraperitoneal exposure)

Single strand breaks

-

(Ueno, Kashimoto et al. 2001)

K-dichromate

-= negative results; + = positive results; ± = weakly positive results

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
Majority of the results from in vivo genotoxicity studies support the conclusion that hexavalent chromium is genotoxic.
Executive summary:

Majority of the results from in vivo genotoxicity studies support the conclusion that hexavalent chromoium is genotoxic.

Chromium-induced DNA damage is thought to be the primary mechanism of chromate genotoxicity and mutagenicity, but it is only clearly observed at doses that are also capable of producing cell death. Recently, data has been presented to the EPA’s Cancer Assessment Review Committee (CARC) to support

mutagenicity as the initiating step in Cr(VI)-induced carcinogenesis. Structural genetic lesions produced by Cr(VI) include DNA adducts, DNA-strand breaks, DNA–protein crosslinks, oxidized bases, abasic sites, and DNA inter- and intrastrand crosslinks()