Dietary administration of ß-ionone epoxide to Sprague-Dawley rats for 90 days.

In a 90-day GLP-compliant study groups of Sprague-Dawley rats (10/sex/group) were fed diets containing ß-ionone epoxide, a fragrance material and a flavoring substance, at dietary concentrations providing target intakes of 0, 20, 40 and 80 mg/kg bw/day. There were no deaths and no adverse changes in clinical observations, ophthalmological examinations, body weight, body weight gain, food consumption, food efficiency; hematology, serum chemistry, urinalysis parameters; or in macroscopic findings attributable to ß-ionone epoxide administration. Increased absolute and relative liver weights in high dose females without correlating hepatic histopathological findings were considered non-adverse. Cortical vacuolation of adrenal zona fasciculata was observed in high-dose males but was considered non-adverse due to the nondegenerative nature of this alteration. ß-Ionone epoxide did not influence estrus cyclicity in females and did not affect sperm morphology or epididymal sperm count, homogenization-resistant spermatid count and motility measurements in male rats. The no-observed-adverse-effect level (NOAEL) for administration of ß-ionone epoxide in the diet was determined to be the highest dose tested of 80 mg/kg bw/day.

Assessment of veterinary drug residues in food: Considerations when dealing with sub-optimal data.

The use of veterinary drugs in food-producing animals may lead to residues in animal-derived foodstuffs, potentially posing a risk to human safety. While the process of veterinary drug residue risk assessment continues to evolve as new data emerges, a recurring challenge is when sub-optimal or incomplete data are provided with the expectation of supporting a robust risk assessment. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) is comprised of international experts who routinely deal with such data challenges when performing veterinary drug residue evaluations. Recent developments in veterinary drug residue risk assessment are described, including specific consequences of sub-optimal data during the risk assessment process. When feasible, practical solutions to such challenges are also highlighted. Case examples from recent JECFA veterinary drug evaluations are provided to clearly quantify and illustrate the concepts described. The information provided is intended to facilitate the generation of improved quality data, enabling more timely and robust veterinary drug residue risk assessments.

Safety evaluation of calcium L-methylfolate.

Calcium L-methylfolate (L-5-MTHF-Ca; CAS Number 151533-22-1) is a source of folate and an alternative to folic acid for use in human food and food supplements. The safety of L-5-MTHF-Ca was evaluated by testing for genotoxicity, subchronic and prenatal developmental toxicity. In in vitro assays L-5-MTHF-Ca was not mutagenic and did not induce other chromosomal events. Additionally, L-5-MTHF-Ca was not genotoxic in the in vivo micronucleus test nor did it induce DNA damage in rat liver cells. In a subchronic toxicity study, rats administered up to 400 mg/kg bw/day of L-5-MTHF-Ca via oral gavage for 13 weeks had no treatment-related mortalities, and no treatment-related effects were identified on behaviour, body weight, food consumption, ophthalmology, haematology, or organ weights. No treatment-related macroscopic or histopathological findings were observed. Calcium and sodium levels increased with increasing dosage, however the slight increases were within historical control ranges and reversible after the recovery period. L-5-MTHF-Ca is neither teratogenic nor embryotoxic. Based on the results of the in vitro and in vivo studies, the safe use of L-5-MTHF-Ca as an ingredient in foods is supported. The no observed adverse effect level was the highest dose in the subchronic toxicity study, i.e. 400 mg/kg bw/day for male and female rats.

Magnesium stearate, a widely-used food additive, exhibits a lack of in vitro and in vivo genotoxic potential.

Magnesium stearate is widely used in the production of dietary supplement and pharmaceutical tablets, capsules and powders as well as many food products, including a variety of confectionery, spices and baking ingredients. Although considered to have a safe toxicity profile, there is no available information regarding its potential to induce genetic toxicity. To aid safety assessment efforts, magnesium sulfate was evaluated in a battery of tests including a bacterial reverse mutation assay, an in vitro chromosome aberration assay, and an in vivo erythrocyte micronucleus assay. Magnesium stearate did not produce a positive response in any of the five bacterial strains tested, in the absence or presence of metabolic activation. Similarly, exposure to magnesium stearate did not lead to chromosomal aberrations in CHL/IU Chinese hamster lung fibroblasts, with or without metabolic activation, or induce micronuclei in the bone marrow of male CD-1 mice. These studies have been used by the Japanese government and the Joint FAO/WHO Expert Committee on Food Additives in their respective safety assessments of magnesium stearate. These data indicate a lack of genotoxic risk posed by magnesium stearate consumed at current estimated dietary exposures. However, health effects of cumulative exposure to magnesium via multiple sources present in food additives may be of concern and warrant further evaluation.

Assessment of the potential health risks associated with the aluminium, arsenic, cadmium and lead content in selected fruits and vegetables grown in Jamaica.

Thirteen Jamaican-grown food crops - ackee (Blighia sapida), banana (Musa acuminate), cabbage (Brassica oleracea), carrot (Daucus carota), cassava (Manihot esculenta), coco (Xanthosoma sagittifolium), dasheen (Colocasia esculenta), Irish potato (Solanum tuberosum), pumpkin (Cucurbita pepo), sweet pepper (Capsicum annuum), sweet potato (Ipomoea batatas), tomato (Solanum lycopersicum) and turnip (Brassica rapa) - were analysed for aluminium, arsenic, cadmium and lead by atomic absorption spectrophotometry and instrumental neutron activation analysis. The fresh weight mean concentrations in these food crops (4.25-93.12 mg/kg for aluminium; 0.001-0.104 mg/kg for arsenic; 0.015-0.420 mg/kg for cadmium; 0.003-0.100 mg/kg for lead) were used to calculate the estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI) and target cancer risk (TCR) for arsenic, associated with dietary exposure to these potentially toxic elements. Each food type had a THQ and HI < 1 indicating no undue non-carcinogenic risk from exposure to a single or multiple potentially toxic elements from the same food. The TCR for arsenic in these foods were all below 1 × 10-4, the upper limit used for acceptable cancer risk. There is no significant health risk to the consumer associated with the consumption of these Jamaican-grown food crops.

Japan Flavour and Fragrance Materials Association's (JFFMA) safety assessment of food-flavouring substances uniquely used in Japan that belong to the class of aliphatic primary alcohols, aldehydes, carboxylic acids, acetals and esters containing additional oxygenated functional groups.

We performed a safety evaluation using the procedure devised by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) of the following four flavouring substances that belong to the class of 'aliphatic primary alcohols, aldehydes, carboxylic acids, acetals, and esters containing additional oxygenated functional groups' and are uniquely used in Japan: butyl butyrylacetate, ethyl 2-hydroxy-4-methylpentanoate, 3-hydroxyhexanoic acid and methyl hydroxyacetate. Although no genotoxicity study data were found in the published literature, none of the four substances had chemical structural alerts predicting genotoxicity. All four substances were categorised as class I by using Cramer's classification. The estimated daily intake of each of the four substances was determined to be 0.007-2.9 µg/person/day by using the maximised survey-derived intake method and based on the annual production data in Japan in 2001, 2005 and 2010, and was determined to be 0.250-600.0 µg/person/day by using the single-portion exposure technique and based on average-use levels in standard portion sizes of flavoured foods. Both of these estimated daily intake ranges were below the threshold of toxicological concern for class I substances, which is 1800 µg/person/day. Although no information from in vitro and in vivo toxicity studies for the four substances was available, these substances were judged to raise no safety concerns at the current levels of intake.

Toxicological evaluation of two novel bitter modifying flavour compounds: 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-hydroxybenzyl)imidazolidine-2,4-dione and 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-hydroxybenzyl)-5,5-dimethylimidazolidine-2,4-dione.

A toxicological evaluation of two novel bitter modifying flavour compounds, 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-hydroxybenzyl)imidazolidine-2,4-dione (S6821, CAS 1119831-25-2) and 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1-(3-hydroxybenzyl)-5,5-dimethylimidazolidine-2,4-dione (S7958, CAS 1217341-48-4), were completed for the purpose of assessing their safety for use in food and beverage applications. S6821 undergoes oxidative metabolism in vitro, and in rat pharmacokinetic studies both S6821 and S7958 are rapidly converted to the corresponding O-sulfate and O-glucuronide conjugates. S6821 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in bone marrow polychromatic erythrocytes in vivo. S7958, a close structural analog of S6821, was also found to be non-mutagenic in vitro. In short term and subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL) for both S7958 and S6821 was 100 mg/kg bw/day (highest dose tested) when administered as a food ad-mix for either 28 or 90 consecutive days, respectively. Furthermore, S6821 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

Food safety risk assessment for estimating dietary intake of sulfites in the Taiwanese population.

The purpose of this study was to assess the health risk associated with dietary intake of sulfites for Taiwanese general consumers by conducting a total diet study (TDS). We evaluated the exposure of Taiwanese to sulfites in the diet and its associated health risk. This study used a list of 128 food items representing 83% of the total daily diet. Among the 128 food items, 59 items may contain sulfites. Samples of the 59 food items were collected and subjected to chemical analysis to determine the sulfur dioxide concentration. Health risk was assessed by calculating the ratio of exposure level to the acceptable daily intake (ADI) level of the analyte. For high-intake consumers, the HI of sulfites was 19.7% ADI for males over the age of three years at the 95th percentile; whereas for females over the age of 66, the HI was 17.8% ADI. The HI for high-intake consumers was above 10% ADI. This suggests that regulatory actions must be continued and that consumers should be advised to be aware of processed foods with relatively high contamination to avoid excessive exposure.

Políticas sanitarias locales puestas a prueba: consultores, expertos, misiones internacionales y poliomielitis en España, 1950-1975 / Local health policies under the microscope: consultants, experts, international missions and poliomyelitis in Spain, 1950-1975

Este trabajo analisa las misiones de expertos de organismos sanitarios internacionales en España destinadas a informar sobre la situación, las actividades realizadas y las intervenciones necesarias en la lucha contra la discapacidad física de los niños. El Plan España-23 fue el instrumento utilizado por la OMS y otras agencias para poner en marcha el proceso de cambio en un país en transformación durante la larga etapa de vigencia de la dictadura franquista. El trabajo utiliza como fuentes informes inéditos de expertos de la OMS, que fueron resultado de visitas realizadas al país entre 1950 y 1975. El abordaje metodológico consistió en un análisis del discurso que se encuentra en las fuentes y su contextualización en los marcos historiográficos pertinentes.

One of the main focuses of analysis of this paper concerns the missions of international health agency experts to Spain to report on the situation, the activities in the fight against physical disabilities in children and on the actions taken to cope with the problem. The Spain-23 Plan was the instrument used by WHO and other agencies to start the process of change in a country undergoing a period of transformation under the enduring Franco dictatorship. As key sources, the paper uses unpublished reports of WHO experts on the subject, which resulted from visits to the country between 1950 and 1975. The methodological approach consists of an analysis of discourses from primary sources within the historiographical framework.

The Japan Flavour and Fragrance Materials Association's (JFFMA) safety assessment of acetal food flavouring substances uniquely used in Japan.

Using the procedure devised by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), we performed safety evaluations on five acetal flavouring substances uniquely used in Japan: acetaldehyde 2,3-butanediol acetal, acetoin dimethyl acetal, hexanal dibutyl acetal, hexanal glyceryl acetal and 4-methyl-2-pentanone propyleneglycol acetal. As no genotoxicity study data were available in the literature, all five substances had no chemical structural alerts predicting genotoxicity. Using Cramer's classification, acetoin dimethyl acetal and hexanal dibutyl acetal were categorised as class I, and acetaldehyde 2,3-butanediol acetal, hexanal glyceryl acetal and 4-methyl-2-pentanone propyleneglycol acetal as class III. The estimated daily intakes for all five substances were within the range of 1.45-6.53 µg/person/day using the method of maximised survey-derived intake based on the annual production data in Japan from 2001, 2005, 2008 and 2010, and 156-720 µg/person/day using the single-portion exposure technique (SPET), based on the average use levels in standard portion sizes of flavoured foods. The daily intakes of the two class I substances were below the threshold of toxicological concern (TTC) - 1800 µg/person/day. The daily intakes of the three class III substances exceeded the TTC (90 µg/person/day). Two of these, acetaldehyde 2,3-butanediol acetal and hexanal glyceryl acetal, were expected to be metabolised into endogenous products after ingestion. For 4-methyl-2-pentanone propyleneglycol acetal, one of its metabolites was not expected to be metabolised into endogenous products. However, its daily intake level, based on the estimated intake calculated by the SPET method, was about 1/15 000th of the no observed effect level. It was thus concluded that all five substances raised no safety concerns when used for flavouring foods at the currently estimated intake levels. While no information on in vitro and in vivo toxicity for all five substances was available, their metabolites were judged as raising no safety concerns at the current levels of intake.

Derivation of safe health-based exposure limits for potential consumer exposure to styrene migrating into food from food containers.

Residual styrene present in polystyrene food packaging may migrate into food at low levels. To assure safe use, safe exposure levels are derived for consumers potentially exposed via food using No/Low Adverse Effect Levels from animal and human studies and assessment factors proposed by European organisations (EFSA, ECHA, ECETOC). Ototoxicity and developmental toxicity in rats and human ototoxicity and effects on colour discrimination have been identified as the most relevant toxicological properties for styrene health assessments. Safe exposure levels derived from animal studies with assessment factors of EFSA and ECHA were expectedly much lower than those using the ECETOC approach. Comparable safe exposure levels were obtained from human data with all sets of assessment factors while ototoxicity in rats led to major differences. The safe exposure levels finally selected based on criteria of science and health protection converged to the range of 90-120 mg/person/d. Assuming a consumption of 1 kg food/d for an adult, this translates to 90 mg styrene migration into 1 kg food as safe for consumers. This assessment supports a health based Specific Migration Limit of 90 ppm, a value somewhat higher than the current overall migration limit of 60 ppm in the European Union.

The JFFMA assessment of flavoring substances structurally related to menthol and uniquely used in Japan.

Using the procedure devised by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), we performed safety evaluations on four flavoring substances structurally related to menthol (L-menthyl 2-methylbutyrate, DL-menthyl octanoate, DL-menthyl palmitate, and DL-menthyl stearate) uniquely used in Japan. While no genotoxicity study data were available in the literature, all four substances had no chemical structural alerts predictive of genotoxicity. Moreover, they all four are esters consisting of menthol and simple carboxylic acids that were assumed to be immediately hydrolyzed after ingestion and metabolized into innocuous substances for excretion. As menthol and carboxylic acids have no known genotoxicity, it was judged that the JECFA procedure could be applied to these four substances. According to Cramer's classification, these substances were categorized as class I based on their chemical structures. The estimated daily intakes for all four substances were within the range of 1.54-4.71 µg/person/day and 60-1250 µg/person/day, using the methods of Maximized Survey-Derived Intake and Single Portion Exposure Technique, respectively, based on the annual usage data of 2001, 2005, and 2010 in Japan. As the daily intakes of these substances were below the threshold of concern applied to class I substances viz., 1800 µg/person/day, it was concluded that all four substances raise no safety concerns when used for flavoring foods under the currently estimated intake levels.

Probabilistic risk assessment of exposure to leucomalachite green residues from fish products.

To assess the potential risk of human exposure to carcinogenic leucomalachite green (LMG) due to fish consumption, the probabilistic risk assessment was conducted for adolescent, adult and senior adult consumers in Taiwan. The residues of LMG with the mean concentration of 13.378±20.56 µg kg(-1) (BFDA, 2009) in fish was converted into dose, considering fish intake reported for three consumer groups by NAHSIT (1993-1996) and body weight of an average individual of the group. The lifetime average and high 95th percentile dietary intakes of LMG from fish consumption for Taiwanese consumers were estimated at up to 0.0135 and 0.0451 µg kg-bw(-1) day(-1), respectively. Human equivalent dose (HED) of 2.875 mg kg-bw(-1) day(-1) obtained from a lower-bound benchmark dose (BMDL10) in mice by interspecies extrapolation was linearly extrapolated to oral cancer slope factor (CSF) of 0.035 (mgkg-bw(-1)day(-1))(-1) for humans. Although, the assumptions and methods are different, the results of lifetime cancer risk varying from 3×10(-7) to 1.6×10(-6) were comparable to those of margin of exposures (MOEs) varying from 410,000 to 4,800,000. In conclusions, Taiwanese fish consumers with the 95th percentile LADD of LMG have greater risk of liver cancer and need to an action of risk management in Taiwan.

The STEP (Safety and Toxicity of Excipients for Paediatrics) database: part 2 - the pilot version.

The screening and careful selection of excipients is a critical step in paediatric formulation development as certain excipients acceptable in adult formulations, may not be appropriate for paediatric use. While there is extensive toxicity data that could help in better understanding and highlighting the gaps in toxicity studies, the data are often scattered around the information sources and saddled with incompatible data types and formats. This paper is the second in a series that presents the update on the Safety and Toxicity of Excipients for Paediatrics ("STEP") database being developed by Eu-US PFIs, and describes the architecture data fields and functions of the database. The STEP database is a user designed resource that compiles the safety and toxicity data of excipients that is scattered over various sources and presents it in one freely accessible source. Currently, in the pilot database data from over 2000 references/10 excipients presenting preclinical, clinical, regulatory information and toxicological reviews, with references and source links. The STEP database allows searching "FOR" excipients and "BY" excipients. This dual nature of the STEP database, in which toxicity and safety information can be searched in both directions, makes it unique from existing sources. If the pilot is successful, the aim is to increase the number of excipients in the existing database so that a database large enough to be of practical research use will be available. It is anticipated that this source will prove to be a useful platform for data management and data exchange of excipient safety information.

Mycotoxins: occurrence, toxicology, and exposure assessment.

Mycotoxins are abiotic hazards produced by certain fungi that can grow on a variety of crops. Consequently, their prevalence in plant raw materials may be relatively high. The concentration of mycotoxins in finished products is usually lower than in raw materials. In this review, occurrence and toxicology of the main mycotoxins are summarised. Furthermore, methodological approaches for exposure assessment are described. Existing exposure assessments, both through contamination and consumption data and biomarkers of exposure, for the main mycotoxins are also discussed.

Multiple mycotoxin exposure determined by urinary biomarkers in rural subsistence farmers in the former Transkei, South Africa.

Subsistence farmers are exposed to a range of mycotoxins. This study applied novel urinary multi-mycotoxin LC-MS/MS methods to determine multiple exposure biomarkers in the high oesophageal cancer region, Transkei, South Africa. Fifty-three female participants donated part of their maize-based evening meal and first void morning urine, which was analysed both with sample clean-up (single and multi-biomarker) and by a 'dilute-and-shoot' multi-biomarker method. Results were corrected for recovery with LOD for not detected. A single biomarker method detected fumonisin B1 (FB1) (87% incidence; mean±standard deviation 0.342±0.466 ng/mg creatinine) and deoxynivalenol (100%; mean 20.4±49.4 ng/mg creatinine) after hydrolysis with ß-glucuronidase. The multi-biomarker 'dilute-and-shoot' method indicated deoxynivalenol-15-glucuronide was predominantly present. A multi-biomarker method with ß-glucuronidase and immunoaffinity clean-up determined zearalenone (100%; 0.529±1.60 ng/mg creatinine), FB1 (96%; 1.52±2.17 ng/mg creatinine), α-zearalenol (92%; 0.614±1.91 ng/mg creatinine), deoxynivalenol (87%; 11.3±27.1 ng/mg creatinine), ß-zearalenol (75%; 0.702±2.95 ng/mg creatinine) and ochratoxin A (98%; 0.041±0.086 ng/mg creatinine). These demonstrate the value of multi-biomarker methods in measuring exposures in populations exposed to multiple mycotoxins. This is the first finding of urinary deoxynivalenol, zearalenone, their conjugates, ochratoxin A and zearalenols in Transkei.

Does EU legislation allow the use of the Benchmark Dose (BMD) approach for risk assessment?

Hazard characterisation is largely based on an approach of (statistically) comparing dose groups with the controls in order to derive points of departure such as no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs). This approach suggests the absence of any relevant effect at the NOAEL. The NOAEL approach has been debated for decades. A recent Scientific Opinion by the European Food Safety Authority (EFSA) concluded that the Benchmark Dose (BMD) approach should be preferred over the NOAEL approach for deriving human (health-based) limit or guidance values. Nonetheless, the BMD approach is used infrequently within European regulatory frameworks. The reason for this may lie in legislation or guidelines requiring the use of the NOAEL approach. In this context, various EU regulatory frameworks were examined on such demands. Interestingly, no single legislation was identified containing statutory requirements in conflict with the use of the BMD approach.

Essential and toxic element concentrations in blood and urine and their associations with diet: results from a Norwegian population study including high-consumers of seafood and game.

The first aim of the study was to evaluate calculated dietary intake and concentrations measured in blood or urine of essential and toxic elements in relation to nutritional and toxicological reference values. The second aim was to identify patterns of the element concentrations in blood and urine and to identify possible dietary determinants of the concentrations of these elements. Adults with a known high consumption of environmental contaminants (n=111), and a random sample of controls (n=76) answered a validated food frequency questionnaire (FFQ). Complete data on biological measures were available for 179 individuals. Blood and urine samples were analyzed for selenium, iodine, arsenic, mercury, cadmium and lead. Principal component analysis was used to identify underlying patterns of correlated blood and urine concentrations. The calculated intakes of selenium, iodine, inorganic arsenic and mercury were within guideline levels. For cadmium 24% of the high consumer group and 8% of the control group had intakes above the tolerable weekly intake. Concentrations of lead in blood exceeded the bench-mark dose lower confidence limits for some participants. However, overall, the examined exposures did not give rise to nutritional or toxicological concerns. Game consumption was associated with lead in blood (B(ln) 0.021; 95%CI:0.010, 0.031) and wine consumption. Seafood consumption was associated with urinary cadmium in non-smokers (B(ln) 0.009; 95%CI:0.003, 0.015). A novel finding was a distinct pattern of positively associated biological markers, comprising iodine, selenium, arsenic and mercury (eigenvalue 3.8), reflecting seafood intake (B 0.007; 95%CI:0.004, 0.010). The study clearly demonstrates the significance of seafood as a source of both essential nutrients and toxic elements simultaneously and shows that exposure to various essential and toxic elements can be intertwined.

Toxicology, occurrence and risk characterisation of the chloropropanols in food: 2-monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol.

Great attention has been paid to chloropropanols like 3-monochloro-1,2-propanediol and the related substance glycidol due to their presence in food and concerns about their toxic potential as carcinogens. The other chloropropanols 2-monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol have been found in certain foods, but occurrence data are generally limited for these compounds. 1,3-dichloro-2-propanol has the most toxicological relevance showing clear carcinogenic effects in rats possibly via a genotoxic mechanism. The dietary exposure to 1,3-dichloro-2-propanol is quite low. Calculated "Margins of Exposure" values are above 10,000. It is concluded that the 1,3-dichloro-2-propanol exposure is of low concern for human health. The toxicology of 2,3-dichloro-1-propanol has not been adequately investigated. Its toxicological potential regarding hepatotoxic effects seems to be lower than that of 1,3-dichloro-2-propanol. Limited data show that 2,3-dichloro-1-propanol occurs only in trace amounts in food, indicating that exposure to 2,3-dichloro-1-propanol seems to be also of low concern for human health. The dietary 2-monochloro-1,3-propanediol burden appears to be lower than that of 3-monochloro-1,2-propanediol. An adequate risk assessment for 2-monochloro-1,3-propanediol cannot be performed due to limited data on the toxicology and occurrence in food. This article reviews the relevant information about the toxicology, occurrence and dietary exposure to the chloropropanols 2-monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol.

Polyethylene glycol-polyvinyl alcohol grafted copolymer: study of the bioavailability after oral administration to rats.

The absorption, urinary excretion, and the biliary excretion of a single oral dose of 10 or 1000 mg/kg bw of (14)C-polyethylene glycol-polyvinyl alcohol (PEG-PVA) grafted copolymer were studied in adult male and female rats. In a balance/excretion experiment, the total excretion of ingested radioactivity was determined over a period of 168 h and residual radioactivity was detected in selected tissues and the carcass. In a biliary excretion experiment, excretion of radioactivity via the bile duct was determined over a period of 48 h after administration of the substance to cannulated rats. Most, if not all, of the radioactivity (>100%) was excreted within 48 h via the feces regardless of sex or dose. Urinary excretion was very limited: 0.45-0.50% of dose at the low dose and 0.22-0.27% of dose at the high dose. At both dose levels, residual radioactivity in the carcass and all organs and tissues after 168 h was ≤ 0.02% of dose. Biliary excretion was 0.01-0.02% of dose. Based on these findings, the bioavailability of PEG-PVA grafted copolymer was determined to be <1% demonstrating that absorption was virtually negligible following a single oral administration to male and female rats.