##### Human Health Risk Assessment of the Pesticide Simplex with the Active Substances Aminopyralid and Fluroxypyr

Line Emilie Sverdrup, Christine Bjørge, Ole Martin Eklo, Merete Grung, Torsten Källqvist, Ingeborg Klingen, Marit Låg, Edgar Rivedal, Erik Ropstad, Steinar Øvrebø

European Journal of Nutrition & Food Safety, Page 1-2
DOI: 10.9734/ejnfs/2022/v14i430488

Simplex is a new herbicide in Norway containing the active substances aminopyralid and fluroxypyr. Aminopyralid is a new active substance in Norway, but fluroxypyr is found in several authorized products. The application concerns use in established grassland for forage, established ley and pasture and in grass at the first year of sowing. The Norwegian Scientific Committee for Food Safety (VKM) has on a request from the Norwegian Food Safety Authority performed a risk assessment on human health of the active substance and the product. The risk assessment of the product was approved at a meeting May 11 2010 by VKMs Scientific Panel on Pesticides (Panel 2). VKM’s Panel 2 concludes as following:

Both Simplex and the active substance aminopyralid are characterized as extremely irritating to the eye based on persistent irritation to the eyes of rabbits. The product Simplex is also found irritating to the rabbit skin.

Aminopyralid has low acute toxicity and is not shown to have genotoxic potential, or to be teratogenic or toxic to the reproduction in animals. There may however be a carcinogenic effect of aminopyralid based on an increased number of uterine sarcomas in mice. The main target organs for sub-chronic and chronic toxicity were the caecum (rats), the stomach (dogs, inflammation) and the liver (dogs, hyperthropy). No adverse effects for chronic toxicity were seen in mice. Rabbit was the most sensitive species for toxicity and the no observed effect levels (NOAELs) derived from studies in this species serve as base for calculations of values for acceptable daily intake (ADI) and acceptable operator exposure level (AOEL).

The estimated risk for operator is assessed as minimal both by use of boom spraying (46% of AOEL) and knapsack sprayers (81% of AOEL).

However, as a result of the hazard classification, a faceshield and gloves are necessary personal protective equipment (PPE) to be worn during mixing and loading operations, due to the risk of serious damage to the eyes and skin irritation.

##### Opinion on the Safety of BioProtein® by the Scientific Panel on Animal Feed of the Norwegian Scientific Committee for Food Safety

Aksel Bernhoft, Knut Gunnar Berdal, Marit Espe, Siri Mjaaland, Ivar Storrø, Henning Sørum, Mette Valheim, Harald Volden, Marit Aursand, Marc Bertnssen, Gro-Ingunn Hemre, Bjørn M. Jenssen, Magny Thommassen, Anne-Katrine Lundbye Haldorsen

European Journal of Nutrition & Food Safety, Page 3-5
DOI: 10.9734/ejnfs/2022/v14i430489

BioProtein® (BP) is a trademark for single cell (bacteria) protein, based on conversion of methane, with the addition of ammonia and oxygen, to a protein source. BP is produced by Norferm AS in Norway, and has been authorized by the EU as a protein source in animal feeds since 1995, for fattening pigs (8%), calves (8%) and salmon (19-33%). Significant immune effects were revealed in a toxicity study performed in rats fed a nucleic acid reduced BP product (NABP) and thereafter, similar, but less severe effects were also found after feeding with untreated BP. Additional studies confirmed increased mesenteric lymph node weights in cats and foxes. Due to the undesirable effects and also due to applications for extended use, BP has been assessed by the Scientific Committee on Animal Nutrition (SCAN) and EU’s Scientific Committee on Food (SCF) in 1995, by SCAN in 2001 and 2003 and by the European Food Safety Authority (EFSA) in 2005. The EU memberstates United Kingdom, France and Finland have also conducted assessments. The EU approval from 1995 remains unchanged.

The Norwegian Food Safety Authority requested the Norwegian Scientific Committee for Food Safety (VKM) to assess the risk of using BP as a protein source in feedingstuffs, both for the animal categories already authorized and for extended use to pet animals, chickens and pigs from weaning to slaughter. The Norwegian Scientific Committee for Food Safety was asked to consider all existing documentation. Based on all documentation enclosed with the request from the Norwegian Food Safety Authority and published scientific articels, an opinion on the safety of BP assessed by the VKM panel on Animal Feed was published on 20 March 2006 (05/608-final-rev1). The Producer made a complaint regarding this opinion and claimed that not all documents on BP had been evaluated. The Norwegian Food Safety Authority then requested VKM to revise its opinion on the risk of using BP as a protein source in feedingstuffs, based on 17 documents previously not available to VKM, in addition to the 20 documents included in the opinion published on 20 March 2006.

BP is composed of a protein with a somewhat different amino acid compostion compared with fish meal, but BP and fish meal have more similarities in amino acid content than soybean meal. BP has relatively high level of nucleic acids, phospholipids, lipopolysaccarides and minerals.

Effect studies with BP have been conducted in rats/mice, pigs, chicken, cats, foxes, and salmon. Most of the concern regarding the side effects of BP in feed is related to the immune response. The main findings include changes in weight and morphology of mesenteric lymph nodes, followed by induction of specific antibodies. Histopathological examination after feeding with NABP also revealed changes in the intestines and several internal organs indicating systemic effects. The Producer claims that the immune response seen in BP-fed mice/rats is most likely a normal response to ingestion of large doses of a foreign antigen, and further, that oral tolerance towards this protein is induced over time. However, these interpretations are not adequately supported by the supplied documentation. A tendency towards adaption might be indicated in some of the studies, other results argue against tolerance induction.

It is unclear whether the content of phospholipids, lipopolysaccarides, nucleic acids or the protein structure, or the combination of these compounds is responsible for the immunological changes observed. However, the particulate structure of BP has been shown to influence the observed immune response as the systemic immune response was avoided by ingestion of BP free of whole cells.

The studies conducted in target species have not included adequate examinations of the immune effects from ingestion of BP. Concerning terrestrial species, no histopathological effects were revealed in the pig, chicken, cat or fox studies. However, increased mesenteric lymph nodes were reported in cats and foxes fed BP. In the remaining studies the main focus has been on production parameters; weight gain, feed intake, feed efficiency, metabolism of nutrients, observation of clinical health, and product quality. When the contents of amino acids were balanced, the inclusion of low levels of BP (9%) tended to stimulate growth in pigs and the same tendency was found in chicken with 6% BP. Higher feed levels of BP tended to cause a reduction in growth.

In salmon, a dose dependent improvement of growth was reported in a short term experiment (8 weeks). However, in longer term experiments with salmon, depressed growth and increased liver weight were observed in freshwater at 19% BP with no-effect-level at 10%. In seawater studies, a tendency of reduced growth was found in salmon fed with 20% BP in the diet, and BP levels of 27% and higher levels resulted in significantly reduced body weight. Furthermore, levels of 27% BP and above in fish feed reduced specific immune responses, but increased lymphocyte response, and also tended to improve the survival after bacterial and viral infections. At 37% BP in the diet histopathological changes in the distal intestine, and reduced storage of glycogen and increased lipid deposition and liver weight were observed. No negative effects were seen in salmon in seawater at a feed level of 13.5% BP. The results indicate negative effects in salmon at BP levels in fish feed considerably lower than those currently approved (19 and 33%, in feed for salmon in fresh and sea water, respectively).

To conclude, in terrestrial target species documented effects of BP include reduced weight gain and increased weight of mesenteric lymph nodes. In the more thoroughly studied species the rat, findings incluse histopathologic effects in mesenteric lymph nodes, changed humoral immune responses, increased weight of other lymphoid tissue (spleen), increased level of neutrophile granulocytes, and slight leakage of hepatic and renal tubuli enzymes. In terrestrial target species, 6% BP in the feed is considered to be the highest inclusion level not to cause such effects. The results from the rat studies show a similar no-effect-level. In salmon, reduced weight gain, liver storage effects, changed humoral and celluar immune responses and histopathological effects in the intestine are documented. A 10% level of BP in fish feed is the highest level tested without causing such effects. There are relatively few valid studies for the risk assessment of BP in target species, and the designs of the assessed studies are very variable. Thus, there are qualitative and quantitative uncertainties concerning the effects of BP in target species. The Panel on Animal Feed is of the opinion that an inclusion level of BP of 6% in the diets to terrestrial target animals and a 10% maximum inclusion level in salmon feed (both for fresh- and seawater stages) would reduce the risk of potentially adverse effects in the animals.

The risk associated with the human consumption of products from animals fed on BP is considered negligible. However, the production of single cell protein for feed production represents a relatively new scientific approach which implies precautionary handling.

##### Risk Assessment of the Fungicide Bontima with the Active Substances Cyprodinil and Isopyrazam

Line Emilie Sverdrup, Christine Bjørge, Ole Martin Eklo, Merete Grung, Torsten Källqvist, Ingeborg Klingen, Marit Låg, Edgar Rivedal, Erik Ropstad, Steinar Øvrebø

European Journal of Nutrition & Food Safety, Page 6-8
DOI: 10.9734/ejnfs/2022/v14i430490

Bontima is a new fungicide containing the two active substances isopyrazam and cyprodinil. Bontima is a fungicide against the most important diseases in winter and spring barley. Isopyrazam is a new active ingredient with new mechanisms of action that may delay the development of fungicide resistance in treated crops.

The risk assessment was finalized at a meeting May 29, 2012, by the Panel on plant protection products of the Norwegian Scientific Committee for Food Safety (VKM).

The Norwegian Food Safety Authority would like, in this regard, an assessment of the following:

• The fate and behaviour in the environment and the ecotoxicological effects and risks with regard to the properties of Bontima and the active substances. The Panel is particularly asked to look at the following: o The persistence of isopyrazam and its metabolites. o The leaching potential of isopyrazam and its metabolites.

VKM’s conclusion is as follows:

Fate-related issues

Isopyrazam is likely to be persistent in Norwegian soils with an associated risk of accumulation after repeated use.

Isopyrazam exhibits low mobility in soil and is not expected to reach groundwater, however the two main metabolites are likely to exceed the EUs drinking water limit of 0.1 $$\mu$$g/L in groundwater.

Since drainage and runoff, as well as drift, contributes to concentrations in surface water the risk assessment have to consider all these sources. In the EU DAR step 4 calculations, buffer zones of 20 m have been used to reduce runoff levels contributions by 80 %. VKM does not accept the use of these buffer zone modifications for Norwegian topographic conditions (with e.g. steeper agricultural areas).

Risk to the environment

There is minimal risk for toxic effects of isopyrazam to terrestrial organisms.

For the aquatic compartment, there is a high risk for toxic effects of isopyrazam to aquatic organisms with the proposed application regime. This is based on calculations of runoff without buffer zone modifications, from which the resulting TER calculations show high risk of acute effects on fish and a medium risk of acute effects on invertebrates. A minimal risk for toxic effects was calculated for sediment dwelling organisms, aquatic plants, and algae.

##### Re-Assessment of the Plant Protection Product PROMAN – with the Active Ingredient Metobromuron [Edition 2]

Marit Låg, Hubert Dirven, Jan Ludvig Lyche, Asbjørn Magne Nilsen, Torsten Källqvist, Katrine Borgå, Ole Martin Eklo, Merete Grung, Line Emilie Sverdrup

European Journal of Nutrition & Food Safety, Page 9-11
DOI: 10.9734/ejnfs/2022/v14i430491

Proman is a broad spectrum selective herbicide for potatoes grown outdoors, containing the active substance metobromuron. VKM’s Panel on Plant Protection Products has previously discussed questions concerning Proman raised by The Norwegian Food Safety Authority, and stated its opinion in a report of 21. January 2015 (http://www.vkm.no/dav/3c64afe035.pdf).

Following this report, The Norwegian Food Safety Authority turned down the application to register Proman as a plant protection product in Norway. The applicant filed a complaint on this decision, and the VKM Panel has been asked to reassess its previous opinion in light of the information given by the applicant in the complaint.

The VKM Panel has discussed the arguments put forward in the complaint. The arguments did not change the Panel’s main conclusions in the original assessment. Some changes in the wording of the conclusions were however done, in order to put more emphasis on areas of uncertainty.

These are the standing conclusions of VKM’s Panel on Plant Protection Products:

On the relevance of the carcinogenic effects observed in the rat carcinogenicity study; fibrosarcomas in females and pheochromocytomas and Leydig cell tumours in males:

It is the opinion of VKM’s Panel for Plant Protection Products that the relevance of the observed incidences of mammary gland tumours and Leydig cell tumours in the rat carcinogenicity study is strengthened by the fact that the increases in tumours associated with exposure to metobromuron are observed in hormone responsive tissues. The panel concludes that the carcinogenic effects observed in the rat carcinogenicity study could be relevant for tumour induction in humans.

Higher incidences of still dumbbell-shaped centres of thoracic vertebrae and nonossification of the 13th rib observed in the rat developmental toxicity study and whether these are considered to be malformations:

VKM’s Panel on Plant Protection Products has discussed the classification of the different types of incomplete ossifications and concluded that incomplete ossification of sternebrae and non-ossification of the 13th rib in rats should by itself be considered to be variations, and not adverse developmental effects. On the other hand, the Panel agrees with ECHA that the “thoracic vertebral centres still dumbbell-shaped” should be considered as malformations, due to limited data and understanding of the mechanism underlying the observed slow reversal of these anomalies. Furthermore, it is the view of the Panel that the different types of retarded ossification induced by the exposure should be considered as a whole when assessing for developmental effects.

Establishment of the NOAEL for the developmental toxicity study in rats and the reference value (ARfD):

VKM’s Panel on Plant Protection Products supports the proposal of an ADI value of 0.008 mg/kg bw/day based on a NOAEL of 0.8 mg/kg bw/day from the 2-year study in mouse, and AOEL of 0.016 mg/kg bw/day based on the NOAEL of 1.6 mg/kg bw/day from the 1-year feeding study in dog. The panel suggests an alternative ARfD value of 0.03 mg/kg bw based on a LOAEL of 10 mg/kg bw /day for the observations of incomplete ossification in the rat developmental study.

The anti-androgenic potential of metobromuron:

The rat carcinogenicity study indicates that metobromuron may interact with the endocrine system. The data from the Hershberger in vivo rat study, the in vitro studies, as well as the comparison with demonstrated effects and mechanisms for flutamide and linuron is suggestive of an anti-androgenic effect. Thus, it is the opinion of the VKM Panel on Plant Protection Products that an anti-androgenic effect of metobromuron cannot be excluded.

##### Risk Assessment of the Pesticide Coragen 20 SC with the Active Substance Chlorantraniliprole

Line Emilie Sverdrup, Christine Bjørge, Ole Martin Eklo, Merete Grung, Torsten Källqvist, Ingeborg Klingen, Marit Låg, Edgar Rivedal, Erik Ropstad, Steinar Øvrebø

European Journal of Nutrition & Food Safety, Page 12-14
DOI: 10.9734/ejnfs/2022/v14i430492

Coragen 20 SC is a new product in Norway containing the active substance chlorantraniliprole. It is applied for use in apples against codling moth (Cydia pomonella), apple fruit moth (Argyresthia conjugella) and free leaf living larvae. The Norwegian Scientific Committee for Food Safety (VKM) was asked by the Norwegian Food Safety Authority to perform a risk assessment on human health, environmental fate and ecotoxicological of the active substance and the product. The risk assessment of the product was approved at a meeting 11th of May 2010 by VKMs Scientific Panel on Pesticides (Panel 2). VKMs Panel 2 concludes as following: The product and the active substance have low acute oral, dermal and inhalation toxicities. Both are non-irritating to the skin, and no allergenic potential by skin contact were shown. Coragen was non-irritating to the eyes, while chlorantraniliprole showed a weak irritating potential.  Chlorantraniliprole is not shown to have any genotoxic or carcinogenic potential, or to be teratogenic or toxic to the reproduction of female animals. The potential for testicular toxicity of chlorantraniliprole is unclear because the study design and the limited number of young dogs (2/sex/group) do not provide basis for a firm conclusion.  No particular target organ for toxicity in any species in the sub-chronic and chronic toxicity studies was seen. The observed dose- and time dependent increased degree of microvesiculation in the zona fasiculata of the adrenal cortex in male rats, is however of uncertain biological significance. All test species (rat, mice, dog) showed physiological adaption to chlorantraniliprole administration (increased liver metabolism with induction of cytochrome P450 enzymes) which was manifested as increased liver weight and hepatocellular hypertrophy. In the chronic toxicity study in mice, the increased liver weight and hepatocellular hypertophy was accompanied with eosinofilic foci, which was assessed as an adverse effect. The no observed effect level (NOAEL) derived from this study serves as basis for calculations of values for acceptable daily intake (ADI) and acceptable operator exposure level (AOEL).

In Panel 2‘s opinion a sub-chronic study (90 days) with the technical material (E2Y45-282) including relevant concentration of the impurity IN-G2S78 should be performed. This would bring information on possible influence of the impurity on the toxicological profile of the technical material, and consequently on the assessment of the NOAELs in the various toxic studies.

The estimated risk for operator and for bystanders or for workers re-entering treated crops is assessed as minimal.

Chlorantraniliprole is persistent in soil with half live of about 1 year. The long half life indicates high potential for accumulation in soil after repeated use, which is confirmed by both model simulations and field studies. The Panel considers field data from the south of Europe not to be relevant for the Nordic conditions based on different climate conditions and soil properties contributing in different directions.

The Panel considers that the existing documentation is not sufficient for a firm conclusion on the use of normalised field data for modelling purposes. However, the substance is persistent and expected to accumulate in soil. The Panel concludes that there is minimal risk for toxic effects on mammals, birds, bees, and microorganisms in soil due to chlorantraniliprole exposure with the proposed exposure regime. Panel concludes that there is “very high risk” for effects on in-field non target arthropods from chlorantraniliprole exposure.

For soil living invertebrates, earthworms seem rather insensitive to chlorantraniliprole and the Panel considers the toxic effects to be minimal. Panel considers the risk for toxic effects on soil living arthropods to be high. Crustaceans and insects larvae are the aquatic organisms most sensitive to chlorantraniliprole.  The Panel concludes that there is a minimal risk of toxic effects on aquatic organisms due to exposure to chlorantraniliprole with the proposed application regime provided that a buffer zone of 30 m to surface water is applied.

##### Factors Contributing to Unsafe Food Processing and Preservation among Food Handlers in Port Harcourt, Nigeria

L. Ekweh Obioma, N. Ojule Inumanye

European Journal of Nutrition & Food Safety, Page 15-27
DOI: 10.9734/ejnfs/2022/v14i430493

Background: Unsafe food processing and preservation among food handlers has been one of the common causes of food and waterborne diseases. This study aimed to identify factors contributing tounsafe food processing and preservation practices among food handlers in Obio-Akpor LGA of Rivers state.

Materials and Methods: The study was a descriptive cross-sectional study whichassessed 365 food handlers in Obio/Akpor Local Government Area of Port Harcourt, Nigeria. A semi-structured questionnaire was used to collect relevant data. Quantitative datawas presented as frequencies and percentages. All statistical tests were set at a significance level of p< 0.05.

Results: Findings show that out of the 365 food handlers who participated in the study, only 43.0% had a set of standard practice guidelines. 47.4% of the food handlers practiced unsafe food processing and preservation methods.Duration of practice for more than 5 years (63.6% vs. 36.4%; p=0.04) and scale of business (large/small) (turnover>NGN50, 000.00) ((58.4%, vs. 10.4%, p=0.05) were significantly associated with unsafe food processing and preservation practicesas handlers who have been in the food business longer and those with larger scale food outlets tended to have better standards.

Conclusion: Unsafe food processing practices exist among food handlers with nearly half of the food handlers studied having poor practices. Inadequate working experience and the presence of more small and medium scale businesses was found to be the factors affecting unsafe food processing and preservation practices in our locality.

##### Evaluation of Proximate Composition, Minerals and Micronutrient Contents of Finger Millet Herbi Dumpling

Deffodile Bharali, Sunita Mishra, Smriti Mishra, Shivani Sinha

European Journal of Nutrition & Food Safety, Page 28-35
DOI: 10.9734/ejnfs/2022/v14i430502

Finger millet is an important crop in Maharashtra, Orissa, and Tamil Nadu. Millet production and consumption have been on the decline for some years. Finger millet samples were gathered from regional locations in Nashik and Kolhapur, Maharashtra. These were also taken as samples for chemical composition and proximate analysis. Standard analytical procedures were used to determine the results. The result of the chemical composition, Nashik (sample one) was found to be Ca mg (6.19), Mg (0.52), Fe (1.09), Zn (1.74± 0.96), Cu (0.10), P (8.90) These findings suggest that finger millet is a good source of calcium and phosphorus. These can be utilised as calcium supplement foods, and their composite flours can be used to preserve a variety of nutrient-dense recipes that can be employed as part of a supplement feeding regimen.