The absorption, distribution, and excreion of [14C] nitrosoproline by rats

Dailey, Robert E.; Braunberg, Robert C.; Blaschka, Andrea M.

doi:10.1016/0300-483x(75)90004-9

Cited by 22 publications

(3 citation statements)

References 8 publications

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“…Blood levels (about 36 μg/g) peaked at 1 h and then rapidly declined to reach < 1 μg/g 24 h after treatment. At 4 h, kidney and liver displayed the highest concentrations (3.5–6 μg/g), but at 24 h negligible values (< 1 μg/g) were detected in all tissues, in line with the rapid NPRO elimination (Dailey et al, 1975 ). Ohshima et al ( 1982 ) reported that rats exposed to single oral doses (5 or 50 μg NPRO/animal, gavage), eliminated about 96% and 3% unchanged NPRO in urine and faeces, respectively, within 24 h after treatment.…”

Section: Assessmentmentioning

confidence: 84%

Risk assessment of N‐nitrosamines in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2023

EFS2

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EFSA was asked for a scientific opinion on the risks to public health related to the presence of Nnitrosamines (N-NAs) in food. The risk assessment was confined to those 10 carcinogenic N-NAs occurring in food (TCNAs), i.e. NDMA, NMEA, NDEA, NDPA, NDBA, NMA, NSAR, NMOR, NPIP and NPYR. N-NAs are genotoxic and induce liver tumours in rodents. The in vivo data available to derive potency factors are limited, and therefore, equal potency of TCNAs was assumed. The lower confidence limit of the benchmark dose at 10% (BMDL 10 ) was 10 μg/kg body weight (bw) per day, derived from the incidence of rat liver tumours (benign and malignant) induced by NDEA and used in a margin of exposure (MOE) approach. Analytical results on the occurrence of N-NAs were extracted from the EFSA occurrence database (n = 2,817) and the literature (n = 4,003). Occurrence data were available for five food categories across TCNAs. Dietary exposure was assessed for two scenarios, excluding (scenario 1) and including (scenario 2) cooked unprocessed meat and fish. TCNAs exposure ranged from 0 to 208.9 ng/kg bw per day across surveys, age groups and scenarios. 'Meat and meat products' is the main food category contributing to TCNA exposure. MOEs ranged from 3,337 to 48 at the P95 exposure excluding some infant surveys with P95 exposure equal to zero. Two major uncertainties were (i) the high number of left censored data and (ii) the lack of data on important food categories. The CONTAM Panel concluded that the MOE for TCNAs at the P95 exposure is highly likely (98-100% certain) to be less than 10,000 for all age groups, which raises a health concern.

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Section: Assessmentmentioning

confidence: 84%

Risk assessment of N‐nitrosamines in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2023

EFS2

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“…In the experiment described here, dietary butterfat did not significantly alter the excretion of NPRO over 24 h following a single oral dose. NPRO is excreted quantitatively in urine and faeces (Dailey et al 1975;Chu & Magee, 1981) and is therefore better suited for this type of study than NDMA which is rapidly metabolized.…”

Section: Discussionmentioning

confidence: 99%

Dietary fat and N-nitrosation in the rat

Ward

Coates²

1987

Br J Nutr

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1. Groups of four conventional (CV) rats ate natural or purified diets either with or without 100 g fat/kg and drank 0.235 M-sodium nitrate. The fats tested were butterfat, coconut oil, olive oil, maize oil and safflower oil.2. Decreased urinary excretion of N-nitrosoproline (NPRO) was observed in rats fed on fat-supplemented diets compared with those fed on low-fat diets, with butterfat having the greatest effect of the fats tested.3. Reduced excretion of NPRO was not the result of inhibition of the intragastric N-nitrosation reaction or absorption of nitrosamine from the gastrointestinal tract.4. The availability of nitrite in aqueous solution was decreased by the fat diets but the effect was similar in all the fats tested.5. Nitrate reductase activity was present in the forestomach contents of CV rats at pH > 4 and was apparently inhibited by feeding a fat diet. No nitrate reductase activity was detected in stomach contents of germ-free rats.6. Nitrate reductase activity in stomach and small intestinal tissue was not altered by feeding a fat diet. 7. It was concluded that nitrate reductase activity in stomach contents was of microbial origin and the decreased urinary excretion of NPRO on feeding the fat diets was mainly due to the inhibition of nitrate reductase activity in stomach contents.Nitrate is commonly present in the diet, the principal source being vegetables which accumulate the ion, e.g. celery (Apium graveolens) and lettuce (Lactuca sativa). It also occurs in tap-water and cured meats. Its potential toxicity depends on its reduction to nitrite by the action of bacterial and mammalian enzymes and the subsequent reactiot) of nitrite with secondary and tertiary amines to form N-nitrosamines. The nitrosation reaction can proceed non-enzymically at acid pH.It was reported by Kato & Kikugawa (1984) that in vitro N-nitrosation of dimethylamine by nitrite was decreased in the presence of unsaturated fatty acid esters. Exploratory experiments in vitro in this laboratory confirmed that N-nitrosation was reduced in the presence of a variety of fats and unsaturated fatty acid esters, but as butterfat was consistently more inhibitory than coconut, olive, maize or safflower oils, the degree of unsaturation did not appear to be a prime factor in the inhibitory process.The experiments reported here were done to investigate whether N-nitrosation in vivo in rats was influenced by dietary fats and, if so, to explore possible mechanisms of inhibition. N-nitrosation in vivo was monitored by measuring urinary excretion of N-nitrosoproline (NPRO), a stable nitrosated amine that is considered to be a reliable index of N-nitrosation reactions in vivo.Although the results of experiments in vivo established that nitrosamine excretion was lower when any of a range of fats was included in the diet, they gave no evidence of inhibition of the nitrosation reaction. Later investigations were therefore directed to the formation and availability of nitrite. Attention was concentrated on butterfat, which was the most effective in lo...

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“…Counts were corrected for quenching effects by referring to a quench correlation curve plotted previously. Procedures used for counting 14 C activity in tissues, carcass, gastrointestinal tract, urine, feces, and expired CO 2 have been described in a previous report (Dailey et al, 1975). In all cases where low activity was encountered in samples, the counting time was adjusted so that the counting error was reduced to 1% or less.…”

Section: Radioactivitymentioning

confidence: 99%

Absorption, distribution, and excretion of [¹⁴C] patulin by rats

Dailey

Blaschka

Brouwer

1977

Journal of Toxicology and Environmental Health

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Adult rats of both sexes were given a single oral dose of [14C] patulin and were sacrificed at various time intervals from 4 hr to 7 days following administration of the mycotoxin. Two groups of rats were employed; the treated group had been exposed to daily oral doses of unlabeled patulin (dissolved in pH 5.0 citrate buffer) in utero and for 41-66 wk after weaning, while the controls were given the buffer only throughout gestation and for 38-81 wk after weaning. Approximately 49% of the administered 14C radioactivity was recovered from feces and 36% from urine within 7 days after dosing. Most of the excretion of labeled material occurred within the first 24 hr. All of the 14C activity detected in the urine samples was either metabolites and/or conjugates of the original [14C]patulin. About 1-2% of the total radioactivity was recovered as 14CO2 from expired air. Carbon-14 radioactivity in various tissues and organs was determined throughout the 7 day period; the most significant retention site was the red blood cells.

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The absorption, distribution, and excreion of [14C] nitrosoproline by rats

Cited by 22 publications

References 8 publications

Risk assessment of N‐nitrosamines in food

Risk assessment of N‐nitrosamines in food

Dietary fat and N-nitrosation in the rat

Absorption, distribution, and excretion of [¹⁴C] patulin by rats

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The absorption, distribution, and excreion of [14C] nitrosoproline by rats

Cited by 22 publications

References 8 publications

Risk assessment of N‐nitrosamines in food

Risk assessment of N‐nitrosamines in food

Dietary fat and N-nitrosation in the rat

Absorption, distribution, and excretion of [14C] patulin by rats

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Product

Resources

About

Absorption, distribution, and excretion of [¹⁴C] patulin by rats