National Toxicology Program

National Toxicology Program
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Abstract for TR-490 - Glutaraldehyde (CASRN 111-30-8)

ABSTRACT

Toxicology and Carcinogenesis Studies of Glutaraldehyde (CAS NO. 111-30-8) in F344/N Rats and B6C3F1 Mice (Inhalation Studies)

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Chemical Formula: C5H8O2

 

Glutaraldehyde is used in large volume in a variety of industries as a disinfectant, preservative, fixative and cross-linking agent, and as a chemical intermediate in the synthesis of pharmaceuticals and pesticides. Glutaraldehyde was nominated by the National Cancer Institute, the Occupational Safety and Health Administration, and the National Institute of Environmental Health Sciences for carcinogenicity studies because of potential occupational exposure. Male and female F344/N rats and B6C3F1 mice were exposed to glutaraldehyde (25% aqueous solution) (approximately 93% pure) by inhalation for 2 years. In vitro genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, and cultured Chinese hamster ovary cells; in vivo studies were conducted to measure sex-linked recessive lethal mutations in Drosophila melanogaster, chromosomal aberrations and micronucleated erythrocytes in mouse bone marrow, and micronucleated erythrocytes in mouse peripheral blood. The results of 13-week inhalation studies with glutaraldehyde were reported previously (NTP, 1993 -- TOX-25 ).

2-YEAR STUDY IN RATS

Groups of 50 male and 50 female F344/N rats were exposed to 0, 250, 500, or 750 ppb glutaraldehyde vapor by inhalation, 6 hours per day, 5 days per week, for 104 weeks. Survival of 500 and 750 ppb female rats was less than that of the chamber controls. Mean body weights of all exposed groups of male rats and 500 and 750 ppb female rats were generally less than those of the chamber controls. Some female rats exposed to 750 ppb were thin to emaciated at the time they were killed moribund. Increased incidences of nonneoplastic nasal lesions occurred primarily within the anterior section of the nose in 500 and 750 ppb rats and to a lesser extent in 250 ppb rats. The more significant lesions included hyperplasia and inflammation of the squamous and respiratory epithelia and squamous metaplasia of the respiratory epithelium.

2-YEAR STUDY IN MICE

Groups of 50 male and 50 female B6C3F1 mice were exposed to 0, 62.5, 125, or 250 ppb glutaraldehyde vapor by inhalation, 6 hours per day, 5 days per week, for 104 weeks. Survival of exposed mice was similar to that of the chamber controls. Mean body weights of female mice exposed to 250 ppb were generally less than those of the chamber controls throughout the study. Incidences of squamous meta-plasia of the respiratory epithelium were increased in 250 ppb males and females and 125 ppb females. Incidences of hyaline degeneration of the respiratory epithelium were increased in all exposed groups of females. The incidence of inflammation of the nose was marginally increased in 250 ppb females.

GENETIC TOXICOLOGY

In genetic toxicity studies, glutaraldehyde was muta-genic with and without S9 metabolic activation in S. typhimurium strains TA100, TA102, and TA104. Glutaraldehyde was mutagenic in mouse L5178Y lymphoma cells in the absence of S9 and induced sister chromatid exchanges in cultured Chinese hamster ovary cells with and without S9. No increase in chromosomal aberrations was induced by glutaraldehyde in cultured Chinese hamster ovary cells with or without S9 at one laboratory; at another laboratory, chromosomal aberrations were induced in the absence of S9 only. Glutaraldehyde did not induce sex-linkedrecessive lethal mutations in germ cells of male D. melanogaster treated as adults by feeding or injection or treated as larvae by feeding. In vivo, glutaraldehyde induced a significant increase in chromosomal aberrations in mouse bone marrow cells 36 hours after a single intraperitoneal injection. In a subset of the 36-hour chromosomal aberrations test, there was a small increase in the number of micronucleated bone marrow polychromatic eryth-rocytes, which was judged to be equivocal. Addi-tional short-term (3-day) and subchronic (13-week) micronucleus tests in mice, using the intraperitoneal or inhalation routes, respectively, yielded negative results.

CONCLUSIONS

Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of glutaraldehyde in male or female F344/N rats exposed to 250, 500, or 750 ppb. There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to 62.5, 125, or 250 ppb.

Incidences of nonneoplastic lesions of the nose were significantly increased in male and female rats and mice.

Synonyms: 1,3-Diformylpropane; glutaral; glutardialdehyde; glutaric dialdehyde; 1,5-pentanedial; 1,5-pentanedione; potentiated acid glutaraldehyde

Trade names: Cidex; Sonacide

 


 

Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of Glutaraldehyde

 

  Male
F344/N Rats
Female
F344/N Rats
Male
B6C3F1 Mice
Female
B6C3F1 Mice
Concentrations Chamber control, 250, 500, or 750 ppb Chamber control, 250, 500, or 750 ppb Chamber control, 62.5, 125, or 250 ppb Chamber control, 62.5, 125, or 250 ppb
Body weights Exposed groups generally less than chamber controls 500 and 750 ppb groups less than chamber controls Exposed groups similar to chamber controls 250 ppb group less than chamber controls
Survival rates 12/50, 14/50, 9/50, 6/50 26/50, 31/50, 15/50, 14/50 31/50, 27/50, 40/50, 38/50 34/50, 37/50, 35/50, 32/50
Nonneoplastic effects Nose: squamous epithelium hyperplasia (3/50, 11/50, 39/50, 48/50); squamous epithelium inflammation (6/50, 17/50, 41/50, 49/50); respiratory epithelium hyperplasia (6/50, 5/50, 17/50, 35/50); respiratory epithelium inflammation (17/50, 10/50, 25/50, 43/50); respiratory epithelium squamous metaplasia (1/50, 2/50, 11/50, 24/50); respiratory epithelium goblet cell hyperplasia (1/50, 0/50, 6/50, 6/50); olfactory epithelium hyaline degeneration (4/50, 8/50, 9/50, 14/50) Nose: squamous epithelium hyperplasia (3/50, 15/50, 29/50, 45/49); squamous epithelium inflammation (6/50, 26/50, 42/50, 48/49); respiratory epithelium hyperplasia (1/50, 6/50, 15/50, 29/49); respiratory epithelium inflammation (5/50, 9/50, 26/50, 42/49); respiratory epithelium squamous metaplasia (1/50, 1/50, 11/50,16/49); respiratory epithelium goblet cell hyperplasia (1/50, 3/50, 5/50, 8/49); olfactory epithelium hyaline degeneration (4/50, 5/50, 12/50, 15/49) Nose: respiratory epithelium squamous metaplasia (2/50, 5/50, 6/50, 9/50) Nose: respiratory epithelium squamous metaplasia (7/50, 11/49, 16/50, 21/50); respiratory epithelium hyaline degeneration (16/50, 35/49, 32/50, 30/50); inflammation (6/50, 7/49, 13/50, 14/50)
Neoplastic effects None None None None
Level of evidence of carcinogenic activity No evidence No evidence No evidence No evidence

 

Genetic Toxicology
Assay Results
Salmonella typhimurium gene mutations: Positive in strains TA100, TA102, and TA104 with and without S9
Mouse lymphoma gene mutations: Positive without S9
Sister chromatid exchanges
Cultured Chinese hamster ovary cells in vitro:

Positive with and without S9
Chromosomal aberrations
Cultured Chinese hamster ovary cells in vitro:

Positive without S9
Mouse bone marrow in vivo: Positive
Sex-linked recessive lethal mutations
Drosophila melanogaster:

Negative
Micronucleated erythrocytes
Mouse bone marrow in vivo:

Equivocal (single-injection protocol); negative (three-injection protocol)
Mouse peripheral blood in vivo: Negative

Report Date: September 1999

Pathology Tables, Survival and Growth Curves from NTP 2-year Studies

Target Organs & Incidences from 2-year Studies


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