Carcinogenicity of Hydrazine and 1,1-Dimethylhydrazine for Mouse Lung

Roe, F. J. C.; Grant, G. A.; Millican, D. M.

doi:10.1038/216375a0

Cited by 101 publications

(26 citation statements)

References 6 publications

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“…The carcinogenicity of hydrazine in the mouse, rat and hamster has been established based on several studies (Biancifiori and Ribacci, 1962); Roe et al, 1967;Severi et al 1968;Kelly, et al, 1969;Biancifiori (1970a); Yamamoto et al, 1970;Toth, 1969 and1972ab;Bhide et al, 1976;Bosan et al, 1987). However, three earlier studies in the hamster have reported no carcinogenicity of hydrazine (Biancifiori, 1970b;Toth, 1972b;MacEwen et al, 1981).…”

Section: Hydrazinementioning

confidence: 99%

Scientific Opinion on the safety of polyvinylpyrrolidone‐vinyl acetate copolymer for the proposed uses as a food additive

2010

EFS2

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The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion on the use of polyvinylpyrrolidone-vinyl acetate (PVP/VA) copolymer in food supplements. PVP/VA copolymer is poorly absorbed orally and largely excreted intact in the faeces. No genotoxicity data are available. Both a 28-day and a 90-day feeding study with PVP/VA copolymer in the rat, revealed a NOAEL of 1000 mg/kg bw/day (highest dose tested). Oral administration of PVP/VA copolymer to male/female rats for 24 months and to male/female dogs for 52 weeks revealed NOAELs of 2800 mg/kg bw/day and 2500 mg/kg bw/day respectively (highest doses tested). No reproductive or developmental toxicity data are available. The exposure to PVP/VA copolymer from its use in food supplements and in pharmaceuticals is 23.4 mg/kg bw/day (adult high consumers) and 16 mg/kg bw/day (child high consumers). The toxicological database was too limited to derive an ADI. From the given range of NOAELs and the intake of PVP/VA copolymer, a Margin of Safety (MOS) varying from 43 to 120 for adults and from 63 to 175 for children can be calculated. These MOS are considered sufficient given the lack of absorption of PVP/VA, the fact that the NOAELs were the highest doses tested and that exposure estimates are based on worst case assumptions. From the maximum residual levels of VA, Margins of Exposure (MOE) of > 10 6 were calculated. The MOE for hydrazine were above 10000. The Panel concluded that the residual levels of hydrazine (up to a maximum of 1.0 mg/kg in the final product) are unlikely to be of safety concern, but considered it would be prudent to lower the level of hydrazine as far as reasonably achievable. The Panel concluded that the use of PVP/VA copolymer in solid food supplements as a binding/coating agent is unlikely to be of safety concern at the proposed uses. © European Food Safety Authority, 2010 KEY WORDSPolyvinylpyrrolidone-vinyl acetate copolymer, CAS Registry Number 25086-89-9, vinyl acetate; polyvinylpyrrolidone; copolyvidon; copovidone; 1-vinyl-2-pyrrolidone-vinyl acetate copolymer; 2-pyrrolidinone, 1-ethenyl-, polymer with ethenyl acetate. SUMMARYFollowing a request from the European Commission, the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on polyvinylpyrrolidone-vinyl acetate (PVP/VA) copolymer when used as a food additive.The present opinion deals with the safety of PVP/VA copolymer for use in food supplements in tablet form as a binding/coating agent in an amount of up to 10% of weight per tablet, for a tablet weight of 1000 mg.PVP/VA copolymer is a copolymer produced by polymerisation of the monomers N-vinyl-2-pyrrolidone (NVP) and vinyl acetate (VA). The substance will be used in food supplement tablets as a binding agent and as a coating agent.No absorption, distribution, metabolism and excretion (ADME) studies were provided by the petitioner. It is reported in literature that PVP/VA copolymer, given its high weight average molecular weight of about ...

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Section: Hydrazinementioning

confidence: 99%

Scientific Opinion on the safety of polyvinylpyrrolidone‐vinyl acetate copolymer for the proposed uses as a food additive

2010

EFS2

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“…Roe et al (1967) intubated a group of 28 female Swiss mice with UDMH doses of 0.5 mg/day, 5 days/week, for 40-60 weeks.…”

Section: Tumorigenicitymentioning

confidence: 99%

Chronic Inhalation Toxicity of Unsymmetrical Dimethylhydrazine: Oncogenic Effects

Haun¹,

Kinkead²,

Gaworski³

et al. 1984

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mentioning

confidence: 99%

“…In contrast, the unsymmetrical isomer did induce pulmonary adenomata in female Swiss mice (Roe, Grant and Millican, 1967) and has recently been shown to induce vascular tumours in lung, kidney and liver of mice of the same strain (Toth, 1972b). 1 -Methylhydrazine (monomethylhydrazine) has been reported not to be car-cinogenic in mice (Kelly and O'Gara, 1965;Roe et al, 1967;Kelly et al, 1969;Mirvish et al, 1969). However, it has recently been reported that the monomethyl derivative increased the incidence of pulmonary adenomata in Swiss mice (Toth, 1972c) and induced malignant histiocytomata of the liver, and increased the incidence of adenomata and adenocarcinomata of the caecum in Syrian golden hamsters (Toth and Shimizu, 1973).…”

mentioning

confidence: 99%

The Alkylation of Nucleic Acids of Rat and Mouse In Vivo by the Carcinogen 1,2-Dimethylhydrazine

Hawks¹,

Magee²

1974

Br J Cancer

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Summary.-l,2-Dimethylhydrazine, in contrast to 1-methylhydrazine, is a potent carcinogen for the colon in rats and mice. 1,2-[14C]Dimethylhydrazine was administered to rats and mice in doses which are carcinogenic following a single dose in the former species, or carcinogenic on repeated administration in the latter species, and the rate of 14CO2 exhalation was measured. Exhalation of 14CO2 was also studied after administration of single doses of 1-['4C]methylhydrazine to mice. Incorporation of radioactivity into the nucleic acids of a variety of organs was found at a time after injection (about 6 h) when 14CO2 production from both compounds was virtually complete. Methylation of nucleic acids of liver and colon, as indicated by the formation of 7-methylguanine, was observed after treatment with 1,2-dimethylhydrazine and to a smaller extent by a factor of about 10 after treatment with 1 -methylhydrazine. Less than 1% of a single dose of 1,2-[14C]dimethylhydrazine was excreted in the bile of rats as determined by chemical and radioactivity assays. The similarities of the biological and biochemical actions of 1,2-dimethylhydrazine with those of some nitroso compounds and of cycasin (methylazoxymethanol glucoside) are emphasized.

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Carcinogenicity of Hydrazine and 1,1-Dimethylhydrazine for Mouse Lung

Cited by 101 publications

References 6 publications

Scientific Opinion on the safety of polyvinylpyrrolidone‐vinyl acetate copolymer for the proposed uses as a food additive

Scientific Opinion on the safety of polyvinylpyrrolidone‐vinyl acetate copolymer for the proposed uses as a food additive

Chronic Inhalation Toxicity of Unsymmetrical Dimethylhydrazine: Oncogenic Effects

The Alkylation of Nucleic Acids of Rat and Mouse In Vivo by the Carcinogen 1,2-Dimethylhydrazine

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