Bone marrow cell chromosomal aberrations and styrene biotransformation in mice given styrene on a repeated oral schedule

Sbrana, Isabella; Lascialfari, D; Rossi, Anna Maria; Loprieno, N.; Bianchi, Marina; Tortoreto, Monica; Pantarotto, C.

doi:10.1016/0009-2797(83)90081-9

Cited by 18 publications

(13 citation statements)

References 21 publications

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“…By reviewing the IARC Monographs, substances were identified with an in vivo genotoxic test with positive response after a single oral or inhalation exposure, or in a few cases (acetamide, bromodichloromethane, chloroform, 1,2-dibromo-3-chloropropane, and methylthiouracil) up to 4 consecutive daily exposures. In the case of acrylamide (Abramsson-Zetterberg 2003), di(2-ethylhexyl)phthalate (Tomita et al 1982), and trichloroethylene (Sbrana et al 1985) lower LEDs for in vivo were identified from other sources than those presented in the IARC monographs.…”

Section: Resultsmentioning

confidence: 99%

Comparison of Carcinogenic and in vivo Genotoxic Potency Estimates

Sanner

Dybing

2005

Basic Clin Pharma Tox

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Mutagenic substances classified as carcinogens are primarily regulated on the basis of their carcinogenic effect. Regulation of mutagens that have not been tested for carcinogenicity represents a problem. In cases where a threshold cannot be identified, the substances may be banned or if their uses are deemed to be unavoidable, the exposure may be reduced to as low as technically and economically feasible. In an attempt to develop a procedure that may be helpful in regulation of mutagenic substances when studies on carcinogenicity are lacking, we have compared the lowest effective dose (LED) giving a response in an in vivo genotoxic test after oral or inhalation exposure with the carcinogenic dose descriptor T25 (the chronic daily dose which will give 25% of the animals tumours above background at a specific tissue site). The 34 carcinogens in the present analysis for which genotoxic mechanisms are likely or possible, represent different classes of carcinogens and different genotoxic endpoints, exhibiting carcinogenic and mutagenic potencies both covering a range of 10,000 between the most and least potent substances. A linear correlation was found between the lowest effective dose for in vivo genotoxicity after oral administration or inhalation exposure and the lowest dose descriptor T25 for tumour formation. The finding that the median of the ratio LED/T25 was 1.05 and that the ratio for 90% of the substances studied fell in the range 0.21 to 9.2 shows that the numerical value of LED is similar to the numerical value of T25 within a factor of 5-10. The results suggest that LED may be used as a basis for regulation of mutagens in cases where a threshold cannot be demonstrated or inferred, and where the substance has not been studied in long-term carcinogenicity studies. In such cases LED divided by a specified assessment factor may represent a virtually safe level or a tolerable risk level for a possible carcinogenic effect.Genotoxic effects are assumed to play an important role in tumour induction of a number of chemicals. Since possible carcinogenic effects have been considered to be more critical than germ cell mutagenesis with regard to chemical mutagens, mutagenic substances classified as carcinogens are primarily regulated on the basis of their carcinogenic effect. Several methods for quantitative hazard and risk characterisation (e.g. the linearised multistage (LMS) model (US EPA 1986), the LED10 method (US EPA 1996), and the T25 method (Sanner et al. 2001) have been used in the regulation of carcinogens.Regulation of mutagens that have not been tested for carcinogenicity, represents a problem. In cases where the genotoxic effect is presumed to exhibit a dose threshold, and the description of the threshold is considered to be robust both from a mode of action point of view and from the available experimental results, a margin of safety approach may be recognised as appropriate for regulation. In cases where a threshold cannot be identified, the substances may be banned or if their uses are deem...

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Section: Resultsmentioning

confidence: 99%

Comparison of Carcinogenic and in vivo Genotoxic Potency Estimates

Sanner

Dybing

2005

Basic Clin Pharma Tox

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“…In a study carried out by Sbrana et al. ( 1983 ), aimed at evaluating the genotoxicity of styrene, a kinetic study was performed in parallel after administration of the compound to mice by gavage at daily doses of 200 mg/kg body weight (bw) for 70 days. Blood was collected on days 1 and 70 at selected time intervals.…”

Section: Assessmentmentioning

confidence: 99%

Safety and efficacy of feed additives consisting of essential oils from the bark and the leaves of Cinnamomum verum J. Presl (cinnamon bark oil and cinnamon leaf oil) for use in all animal species (FEFANA asbl)

Bampidis¹,

Azimonti²,

Bastos³

et al. 2022

EFS2

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Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of essential oils from the bark and the leaves of Cinnamomum verum J. Presl (cinnamon bark oil and cinnamon leaf oil), when used as sensory additives (flavourings) in feed and water for drinking for all animal species. Owing to the presence of styrene in the essential oils under assessment, the FEEDAP Panel is not in the position to conclude on the safety for long‐living animals and animals for reproduction. For ‘short‐living’ animals, the FEEDAP Panel concluded that cinnamon bark oil and cinnamon leaf oil are considered as safe up to the maximum proposed use levels in complete feed. For ‘short‐living’ animals, the Panel considered the use of cinnamon bark oil in water for drinking as safe provided that the total daily intake of the additive does not exceed the daily amount that is considered safe when consumed via feed. For cinnamon leaf oil, the proposed use level in water for drinking of 3 mg/L is considered as safe for ‘short‐living’ animals. No concerns for consumers were identified following the use of the additives at the use level considered safe in feed for the target species. Based on the presence of safrole ≥0.1%, cinnamon leaf oil and bark oil are classified as carcinogen (category 1B) and handled accordingly. The use of the additives under the proposed conditions in animal feed was not expected to pose a risk for the environment. Since C. verum and its preparations are recognised to flavour food and its function in feed would be essentially the same, no further demonstration of efficacy is considered necessary for cinnamon essential oils.

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“…These studies showed positive results for markers of DNA damage (DNA-adducts, single-strand breaks detected by Comet assay and SCE), while negative or weakly positive results were reported for chromosomal damage (structural chromosomal aberrations and micronuclei). Two in vivo oral studies described in the IARC Monograph reported negative results for chromosomal aberrations in bone marrow of male and female mice exposed up to the maximum tolerated doses, after single or repeated administrations (Loprieno et al, 1978;Sbrana et al, 1983). In one of these oral studies, separate experiments carried out in parallel with styrene oxide at the same range of doses showed a statistically significant dose-related increase in chromosomal aberrations (Loprieno et al, 1978).…”

Section: Genotoxicity Of Styrenementioning

confidence: 99%

Assessment of the impact of the IARC Monograph Vol. 121 on the safety of the substance styrene (FCM No 193) for its use in plastic food contact materials

Silano¹,

Baviera²,

Bolognesi³

et al. 2020

EFS2

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The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids ( CEP ) was requested by the European Commission to re‐evaluate the safety of styrene ( FCM No 193) for use in plastic food contact materials ( FCM ) following the classification by the International Agency for Research on Cancer ( IARC ) as ‘probably carcinogenic to humans’. The IARC Monograph pertains to hazard identification, based on studies on high‐dose occupational exposures by inhalation and animal studies, also mainly by inhalation. The Panel considered that the IARC conclusions cannot be directly applied to the evaluation of risks for consumers from the oral exposure to styrene, but also concluded that, based on the data provided in the IARC Monograph and by the industry, a concern for genotoxicity associated with oral exposure to styrene cannot be excluded. The migration of styrene into foods packed in styrenic plastics is below 10 μg/kg for the majority of the foods, but up to 230 μg/kg was reported. Migration tends to be high for contact with fatty foods, and/or with high surface to volume ratios of the FCM . Dietary exposure of the consumers to styrene migrating from styrenic plastics was estimated in the order of 0.1 μg/kg body weight (bw) per day. It is in the same range as exposure from styrene present in foods as such. The dietary exposure (food component plus migration from styrenic plastics) is similar or lower than that by inhalation in the general population. Taking the human exposure data into account, the Panel concluded that a systematic review of genotoxicity and mechanistic data, comparative toxicokinetics and analysis of species differences is required for assessing the safety of styrene for its use in FCM .

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Bone marrow cell chromosomal aberrations and styrene biotransformation in mice given styrene on a repeated oral schedule

Cited by 18 publications

References 21 publications

Comparison of Carcinogenic and in vivo Genotoxic Potency Estimates

Comparison of Carcinogenic and in vivo Genotoxic Potency Estimates

Safety and efficacy of feed additives consisting of essential oils from the bark and the leaves of Cinnamomum verum J. Presl (cinnamon bark oil and cinnamon leaf oil) for use in all animal species (FEFANA asbl)

Assessment of the impact of the IARC Monograph Vol. 121 on the safety of the substance styrene (FCM No 193) for its use in plastic food contact materials

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