Reactivity and fate of benzene and formaldehyde in culture medium with and without fetal calf serum; relevance to in vitro mutagenicity testing

Proctor, Bertha L.; Gaulden, Mary Esther; Dowd, Mary Ann

doi:10.1016/0027-5107(86)90136-3

Cited by 18 publications

(6 citation statements)

References 15 publications

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“…Catechol and hydroquinone (or their metabolites) can be concentrated in bone marrow and lymphoid organs (200), and reports suggest that the toxicity of benzene may be related to the concentration of catechol and hydroquinone in bone marrow (26). In addition, benzene is so volatile that one study showed that 90% of a 250-ppm solution was lost to the head space after 1 hr at 24 ?C; however, benzene did not appear to react with the culture medium with or without fetal calf serum (201 tions, SCEs, and mieronuclei, but does not cause gene mutations. In addition, benzene is so volatile that one study showed that 90% of a 250-ppm solution was lost to the head space after 1 hr at 24 ?C; however, benzene did not appear to react with the culture medium with or without fetal calf serum (201 tions, SCEs, and mieronuclei, but does not cause gene mutations.…”

Section: Genetic Toxicologymentioning

confidence: 85%

Multiple-Site Carcinogenicity of Benzene in Fischer 344 Rats and B6C3F 1 Mice

Huff¹,

Haseman²,

DeMarini³

et al. 1989

Environmental Health Perspectives

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Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3F1 mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3F1 mice, and female B6C3F1 mice. In male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. In female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Genetic Toxicologymentioning

confidence: 85%

Multiple-Site Carcinogenicity of Benzene in Fischer 344 Rats and B6C3F 1 Mice

Huff¹,

Haseman²,

DeMarini³

et al. 1989

Environmental Health Perspectives

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“…The results strongly indicate that the respective growth supplements reacted with formaldehyde, and therefore influenced the results. In cell-free experiments, formaldehyde was previously shown to react easily with serum (Proctor et al, 1986), and formaldehyde metabolism and excretion are known to involve reaction with thiols, e.g., glutathione and cysteine. The complete formulations of the fibroblast media HSM and LSM contain approximately 200-fold and 25-fold higher amounts of protein, respectively, than the epithelial cell media BEG and EMA, due to the respective requirements of these cell types for serum or PEX (cf .…”

Section: Discussionmentioning

confidence: 99%

Toxicity of Formaldehyde to Human Oral Fibroblasts and Epithelial Cells: Influences of Culture Conditions and Role of Thiol Status

et al. 1998

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The toxicity of formaldehyde, a monomer released from certain polymeric dental materials, was studied in cultured human oral fibroblasts and epithelial cells. The influences of growth conditions were evaluated for both cell types, as well as the role of the internal and external thiol states. A one-hour exposure to formaldehyde decreased the colony-forming efficiency (CFE) of both cell types in a concentration-dependent manner, although the toxicity varied up to 100-fold with the conditions. Clearly, the presence of serum and the thiol cysteine counteracted the toxicity in fibroblasts. Similarly, pituitary extract and cysteine, or a mixture of amino acids and ethanolamines, counteracted the formaldehyde toxicity in serum-free cultures of epithelial cells. In contrast, a growth-promoting surface matrix of fibronectin and collagen did not influence the formaldehyde toxicity, as shown by both the CFE assay and a dye reduction assay. Further, a short-term change to the various growth media per se with or without the supplements serum or cysteine did not significantly alter the CFE. Analysis of the thiol state demonstrated significant differences between epithelial cells and fibroblasts, i.e., comparatively lower cellular levels of the free low-molecular-weight thiols glutathione and cysteine in fibroblasts. This result correlated to significantly higher formaldehyde toxicity in the fibroblasts than in the epithelial cells. Taken together, the results indicated the cytoprotective function of both intracellular and extracellular thiols toward formaldehyde, as well as the usefulness of thiol-free and chemically defined conditions for toxicity assessments in oral epithelial cells and fibroblasts. We conclude that the combined use of a controlled external milieu and the presumed target cell type may be advantageous in evaluations of oral toxicity mechanisms or the toxic potency of dental materials, particularly those which, like formaldehyde, may react with thiols or amines.

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“…In addition, benzene is so volatile that one study showed that 90% of a 250-ppm solution was lost to the head space after 1 hr at 24°C; however, benzene did not appear to react with the culture medium with or without fetal calf serum (201).…”

Section: Genetic Toxicologymentioning

confidence: 99%

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Huff

Haseman

DeMarini

et al. 1989

Environ Health Perspect

113

107

View full text Add to dashboard Cite

Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3FW mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previ. ous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals.For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3FW mice, and female B6C3FM mice. In male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. In female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity. In male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas, malignant lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined), Harderian gland adenomas, and squamous cell carcinomas of the preputial gland. In female mice, benzene caused increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benign mixed tumors, carcinomas and careinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcin...

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Reactivity and fate of benzene and formaldehyde in culture medium with and without fetal calf serum; relevance to in vitro mutagenicity testing

Cited by 18 publications

References 15 publications

Multiple-Site Carcinogenicity of Benzene in Fischer 344 Rats and B6C3F 1 Mice

Multiple-Site Carcinogenicity of Benzene in Fischer 344 Rats and B6C3F 1 Mice

Toxicity of Formaldehyde to Human Oral Fibroblasts and Epithelial Cells: Influences of Culture Conditions and Role of Thiol Status

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

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