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PubMedDate not supplied

Comparisons of protein changes in human and rodent hepatocytes induced by the rat-specific carcinogen, methapyrilene.

There is a growing concern that the rodent bioassay may not always serve as an appropriate model to assess the carcinogenic risk for humans exposed to certain compounds. Mechanistic research that examines the effects of a compound in rodent and man could help in the interpretation of bioassay results. This paper reports a novel use of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) technology to assess similarities and differences in the response of rodents and humans to the rat-specific hepatocarcinogen, methapyrilene (MP). A sequential examination of rodent and human hepatic proteins was conducted following in vivo exposure of rats and mice and in vitro exposure of rat, mouse, and human hepatocytes to MP. Results showed that covalent modifications observed in rats and mice in vivo were duplicated both qualitatively and quantitatively in the corresponding in vitro systems and that these modifications correlated with carcinogenic susceptibility. Covalent modifications in human hepatocytes were minimal despite exposure to concentrations of MP that were 6-fold higher than those used in rodent hepatocytes. These studies suggest that in the case of MP the rat is not the most appropriate model for assessing the human situation. Furthermore, these data show that in vitro-in vivo comparisons based on 2-D PAGE may provide adjunctive information for extrapolating rodent toxicity/bioassay results to human risk assessment.

Animals↗
PubMed1995

Incorporation of 5-iodo-2'-deoxyuridine and 5-bromo-2'-deoxyuridine into rodent DNA as determined by neutron activation analysis.

Using 5-iodo-2'-deoxyuridine (IdU) and 5-bromo-2'-deoxyuridine (BrdU) as DNA precursors, neutron activation analysis (NAA) of iodine and Br was developed as a quantitative method for determining DNA synthesis. Endogenous rodent tissue concentrations of bromine (Br) and iodine ranged 100-fold from a low of 0.06 microgram of iodine/g of rat gastrointestinal tract (GIT) to a high of 5.99 micrograms of Br/g of rat kidney. All 10 rodent tissues had concentrations of Br 4 to 76 times higher than those of iodine. Rat hepatic Br concentrations could be reduced 17-fold by dietary and pharmacological methods. Female Fischer 344 rats and male C57BL/6 mice were given 4-8 intraperitoneal injections of either IdU or BrdU as a DNA precursor. Tissue clearance of iodine in IdU-treated rodents was both faster and more complete (in mice 4 and in rats 17 h or less) than Br clearance from BrdU-treated rodents (at 162 h nonincorporated Br label still remains). In rat liver, lung, and kidney, the iodine label incorporated from IdU into DNA was stable for at least 162 h. The incorporation ratio is defined as the microgram halogen/tissue for either IdU- or BrdU-treated rodents divided by the microgram halogen/g tissue of untreated rodents. NAA-based studies of DNA synthesis gave high incorporation ratios in rat liver (5.3), rat lung (6.7), rat GIT (19.0), rat spleen (24.0), mouse GIT (10.1), and mouse spleen (25.8).

Animals↗
PubMed1998

Molinate: rodent reproductive toxicity and its relevance to humans--a review.

Molinate is a thiocarbamate herbicide used on rice. During the evaluation of the compound for regulatory compliance, an adverse effect on male reproduction in rats was observed. This led to extensive investigations in rats, mice, rabbits, dogs, monkeys, and humans, resulting in a description of the cause of the effect and establishing an empirical case for rodent specificity. More recent investigations have also shown an effect on the ovaries in rodents. A series of investigations into the mechanism of action to support the view that the effect was specific to rodents has been concluded. The results from this investigation are drawn together and show that the mode of action is via a metabolite, the sulfoxide, which is primarily found in rodents, and that the lesion in both rodent sexes is elicited via inhibition of the enzyme neutral cholesterol ester hydrolase, resulting in interference with mobilization of cholesterol from high-density lipoprotein, a path specific to rodents. Thus, the mechanism of action is such that the effect cannot be elicited in other species including humans.

Animals↗
PubMed1996

Sporadic amplification of ID elements in rodents.

ID sequences are members of a short interspersed element (SINE) repetitive DNA family within the rodent genome. The copy number of individual ID elements varies by up to three orders of magnitude between species. This amplification has been highly sporadic in the order Rodentia and does not follow any phylogenetic trend. Using library screening and dot-blot analysis, we estimate there are 25,000 copies of ID elements in the deer mouse, 1,500 copies in the gerbil (both cricetid rodents), and 60,000 copies of either ID or ID-like elements in a sciurid rodent (squirrel). By dot-blot analysis, we estimate there are 150,000, 4,000, 1,000, and 200 copies of ID elements in the rat, mouse, hamster, and guinea pig, respectively (which is consistent with previous reports) and 200 copies in the hystricognath rodent, nutria. Therefore, a rapid amplification took place not only after the divergence of rat and mouse but also following the deer mouse (Peromyscus) and hamster split, with no evidence of increased amplifications in hystricognath rodents. No notable variations of sequences from the BC1 genes of several myomorphic rodents were observed that would possibly explain the varied levels of ID amplification. We did observe subgenera and species-group-specific variation in the ID core sequence of the BC1 gene within the genus Peromyscus. Sequence analysis of cloned ID elements in Peromyscus show most ID elements in this genus arose prior to Peromyscus subgenus divergence. Correspondence of the consensus sequence of individual ID elements in gerbil and deer mouse further confirms BC1 as a master gene in ID amplification. Several possible mechanisms responsible for the quantitative variations are explored.

Animals↗
PubMed1990

Relationships between body temperature, thermal conductance, Q10 and energy metabolism during daily torpor and hibernation in rodents.

In the present paper we examine the ability of rodents to maintain body temperature (TB) following the marked reductions in metabolic heat production associated with torpor. Previously published values for metabolic rate (M), TB and ambient temperature (TA) were used to calculate thermal conductances (C') during normothermy and torpor in rodents capable of daily torpor (11 species) and hibernation (18 species). Values of C' for torpid animals are uniformly lower than C' in normothermic animals. In addition, C' of normothermic and torpid rodents decreases with increasing body mass (BM). However, the slope of the relationship between C' and BM is almost 4-fold greater for normothermic than for torpid animals. Thus, the ability of torpid rodents to conserve body heat by reducing C' decreases with increasing mass. Rodents that use daily torpor tend to be small and they tend to maintain TB well above TA during torpor. Hibernators tend to be larger and regulate TB relatively close to TA. Thus, the reductions in C' appear to be closely correlated with the level of TB regulation during torpor. We suggest that the changes in C' represent a suite of physiological adaptations that have played a central role in the evolution of torpor, enabling rodents to regulate TB above TA during periods of very low heat production. Based on the approach used here we address the controversy of whether reductions in M during torpor are due entirely to temperature effects or whether metabolic inhibition in addition to temperature effects may be important. We suggest that the controversy has been confused by using Q10 to evaluate the relationship of M and TB in endotherms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed2006

Relevance of rodent models of intravenous MDMA self-administration to human MDMA consumption patterns.

RATIONALE: Despite decades of research specifying harmful effects produced by 3,4-methylenedioxymethamphetamine (MDMA; a principal component of 'ecstasy' pills), young people (and adults) continue to use it. In an attempt to model human MDMA consumption patterns, preclinical investigators have sought to establish reliable patterns of intravenous MDMA self-administration in rodents. OBJECTIVE: The objective of this report is to offer a critical review of published data (including our own novel findings) that reveal MDMA self-administration in rodents. RESULTS: The data indicate that MDMA serves as a reinforcer in rodents, though the responses are not similar to those previously reported for psychostimulants (i.e., cocaine). Important differences between rodent models and human use patterns include frequency of dosing and dosage exposure, routes of administration, tolerance that develops to MDMA after repeated exposure, polydrug use in humans but not by rodents, limits on the repertoire of behaviors that can be exhibited by rodents undergoing IV self-administration procedures, and the question of neurotoxicity as it relates to models of self-administration. CONCLUSIONS: While MDMA is not as potent a reinforcer as other drugs of abuse, the fact remains that young people and adults continue to use the drug, and therefore, additional research is needed to determine why drugs with low reinforcing effects continue to be abused.

Animals↗
PubMed2006

Parasites of two abundant sympatric rodent species in relation to host phylogeny and ecology.

In the present study, two abundant sympatric rodent species (27 Apodemus flavicollis and 33 A. sylvaticus) were studied for their endo- and ectoparasite fauna. The rodents were trapped in Dormagen, a city in North Rhine-Westphalia, Germany. A total of 20 different parasites species were identified, 13 endoparasite (2 Digenea, 5 Cestoda and 7 Nematoda) and 7 ectoparasite (5 Insecta and 2 Arachnida) species. Thirteen parasite species were found inhabiting both rodent species. The predominant endoparasite species in both rodents was the nematode Pelodera strongyloides, followed by the nematode Heligmosomoides polygyrus and a Syphacia species. The flea Ctenophthalmus agyrtes was the dominant ectoparasite in both rodent species. A. flavicollis usually carried 1-7 ecto-/endoparasite species (mean 4.0), whereas A. sylvaticus were mostly infested with 1-9 (mean 4.4). The parasite diversity of A. flavicollis (H' = 0.268, J = 0.097) was marginal lower in comparison to A. sylvaticus (H' = 0.319, J = 0.110). The two rodent species examined show remarkable similarities in the composition of their endo- and ectoparasite fauna being directly related to their similar pattern of living in the investigated area.

Animals↗
PubMed2006

Seasonal variations in detecting Borrelia burgdorferi sensu lato in rodents from north eastern Austria.

Austria is well known as an endemic area of Lyme borreliosis. To assess the annual variation of rodent populations that may host agents of Lyme borreliosis we collected rodents in northeastern Austria. Life traps were set out every six weeks during a year consecutively in one each of the three different zones (Hohenau, Ernstbrunn, Vienna Woods) that cover the main habitat characteristics of small mammals in northeastern Austria. Rodents were collected and identified. Samples of heart, urine bladder and brain were removed under aseptic conditions for cultivation of borrelia. Samples of heart muscle were additionally used for molecular detection of borrelia by Real-Time polymerase chain reaction. PCR was performed with borrelia universal primers and with species-specific primers. 938 mice were caught, most frequently Apodemus flavicollis (44%), followed by Clethrionomys glareolus (35%), Microtus arvalis (9%), A. sylvaticus (7%) and Mus musculus (6%). Significant differences were seen in the total number of catch per area (Hohenau, Ernstbrunn, Vienna Woods equal 10:9:2) and in the distribution of the various rodent species in the respective areas. Borrelia strains were grown from only 65 (7%) animals, and more frequently isolated from bladder wall than from heart muscle, and only once from brain. Heart specimens of 223 animals were positive by borrelia PCR (24%), most frequently of the rodent species A. flavicollis (43%) and C. glareolus (38%). Borrelia afzelii was most frequently identified, followed by B. burgdorferi sensu stricto, B. garinii and by mixed infection of B. afzelii with B. burgdorferi sensu stricto. B. garinii was most frequently detected in heart samples of A. sylvaticus (about 20%). In about 3% of PCR positive samples the identification of one of the three mentioned genospecies of borrelia could not be ascertained with the test panel used. The results confirm the rodent species A. flavicollis, A. sylvaticus, M. arvalis and C. glareolus as reservoir animals for B. afzelii, B. garinii and B. burgdorferi sensu stricto, agents of Lyme borreliosis. Notable is the salient presence of B. garinii in heart specimens of A. sylvaticus.

Animals↗
PubMed2002

Rodent allergens.

Rodent allergens play a significant role in the pathogenesis of asthma and allergic rhinitis, and are potent causes of acute and chronic symptoms. This has long been apparent in occupational settings, particularly in the laboratory, but has been most recently studied and found to be important in home environments. These allergens have been suggested as uniquely important among inner-city children with asthma. Furthermore, rodents have become increasingly popular as pets. With recent awareness of significant exposure in a variety of settings, hypersensitivity to rodents has become increasingly important. This review focuses on the importance of rodent allergens, concentrating on mouse and rat, but including other potentially important rodents such as gerbil, hamster, and rabbit. It also discusses the pathogenesis, diagnosis, prevention, and management of rodent allergy.

Allergens↗
PubMed1981

An immunological characterization of the basic proteins of rodent sciatic nerve myelin.

Radioimmunoassays (RIA) for the myelin basic protein (MBP) and P2 protein together with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to establish the identities of and relationships between the basic proteins (BP) of rodent peripheral nervous system (PNS) myelin. The PNS myelin proteins studied, in order of increasing mobility of SDS-PAGE, are P1, PR (R = rodent) and PB (B = breakdown). The majority of the acid extractable proteins of rodent PNS myelin are MBP related as shown by MBP-RIA. When tested individually, rodents P1, PR and PB were each found to cross-react in the RIA for MBP but not that for P2. The acid extracts of rodent PNS myelin were found to contain P2, although in minute quantities. P2 accounts for approximately 0.05-1.0% of the acid extractable protein in rodent PNS myelin.

Animals↗
PubMed1992

Predictive assay for rodent carcinogenicity using in vivo biochemical parameters: operational characteristics and complementarity.

111 chemicals of known rodent carcinogenicity (49 carcinogens, 62 noncarcinogens), including many promoters of carcinogenesis, nongenotoxic carcinogens, hepatocarcinogens, and halogenated hydrocarbons, were selected for study. The chemicals were administered by gavage in two dose levels to female Sprague-Dawley rats. The effects of these 111 chemicals on 4 biochemical assays (hepatic DNA damage by alkaline elution (DD), hepatic ornithine decarboxylase activity (ODC), serum alanine aminotransferase activity (ALT), and hepatic cytochrome P-450 content (P450)) were determined. Composite parameters are defined as follows: CP = [ODC and P450), CT = [ALT and ODC), and TS = [DD or CP or CT]. The operational characteristics of TS for predicting rodent cancer were sensitivity 55%, specificity 87%, positive predictivity 77%, negative predictivity 71%, and concordance 73%. For these chemicals, the 73% concordance of this study was superior to the concordance obtained from published data from other laboratories on the Ames test (53%), structural alerts (SA) (46%), chromosome aberrations in Chinese hamster ovary cells (ABS) (48%), cell mutation in mouse lymphoma 15178Y cells (MOLY) (52%), and sister-chromatid exchange in Chinese hamster ovary cells (SCE) (60%). The 4 in vivo biochemical assays were complementary to each other. The composite parameter TS also shows complementarity to all 5 other predictors of rodent cancer examined in this paper. For example, the Ames test alone has a concordance of only 53%. In combination with TS, the concordance is increased to 62% (Ames or TS) or to 63% (Ames and TS). For the 67 chemicals with data available for SA, the concordance for predicting rodent carcinogenicity was 47% (for SA alone), 54% (for SA or TS), and 66% (for SA and TS). These biochemical assays will be useful: (1) to predict rodent carcinogenicity per se, (2) to 'confirm' the results of short-term mutagenicity tests by the high specificity mode of the biochemical assays (the specificity and positive predictivity are both 100%), and (3) to be a component of future complementary batteries of tests for predicting rodent carcinogenicity.

Alanine Transaminase↗
PubMed1990

Polyomavirus-based shuttle vectors for studying mechanisms of mutagenesis in rodent cells.

We have constructed a series of polyomavirus-based shuttle vectors for analyzing mechanisms of mutagenesis in rodent cell systems. These vectors contain the supF suppressor tRNA gene which serves as the mutagenesis target; the pBR327 replication functions and ampr gene for replication and selection in bacteria; and the polyomavirus genome which permits replication in rodent cells. The polyoma genomes used in these vectors vary in their enhancer regions, causing varying efficiencies of replication in different types of rodent cells. One of the vectors (pPySLPT-2) which replicates particularly well in several different rodent cell types (i.e., Chinese hamster ovary, mouse hepatoma and mouse lymphoma) was used to compare mutation induction by UV radiation in UV repair-deficient mouse lymphoma L5178Y-R cells with mutagenesis in the related UV repair-proficient line, L5178Y-S. In both cell types, UV-induced mutants could be recovered at frequencies up to 50-fold higher than that of the spontaneous background. At a given UV fluence the L5178Y-R cells were more highly mutable than the L5178Y-S cells. Our results indicate that these new polyomavirus-based vectors should be useful for analysis of the molecular mechanisms of mutation induction in rodent cell systems, and in particular should allow detailed analysis of mutagenesis in the well characterized rodent somatic cell mutants.

Animals↗
PubMed1995

Comparison of repetitive elements in the third intron of human and rodent mitochondrial benzodiazepine receptor-encoding genes.

The third intron of the mitochondrial benzodiazepine receptor (MBR)-encoding gene was sequenced from hamster, mouse and human. The rodent species were found to include an Alu-like sequence, as was first discovered in the rat gene. Differences with the rat intron were evident by an insertion of an additional B1 element in the hamster and the introduction of a complete and two partial B2 sequences in the mouse intron. The human intron contained a cluster of four Alu sequences; however, all of these repetitive elements were found to be in the opposite orientation relative to the Alu-like sequence present in the rodent genes. These findings support the possibility that the rodent Alu-like sequence is a remnant of a retropositional insertion in this gene prior to the divergence of rodent species. Because the human intron does not contain the same Alu remnant, it cannot be concluded that the rodent sequence represents an insertion of a primordial Alu element prior to the divergence of rodent and primate lineages.

Animals↗
PubMed2004

Blood glucose concentration in caviomorph rodents.

Hystricomorph rodents are a group of species that belong to the suborder Hystricognathi. They mainly inhabit South American (caviomorph) and African (phiomorph) habitats. This group of rodents has a divergent insulin structure. For example, insulin in this group of rodents exhibits only 1-10% of biological activity in comparison to other mammals. Therefore, hystricomorph rodents may hypothetically be unable to regulate blood glucose concentration as non-hystricomorph mammals. In this work we evaluated blood glucose concentration in nine species of caviomorph rodents, with emphasis on species belonging to the families Abrocomidae, Ctenomyidae and Octodontidae. Specifically we: (1) measured glucose concentrations after a fasting period; and (2) conducted a glucose tolerance test. In the latter assay we used Octodon degus as a representative species of the genus Octodon. Results showed that blood glucose concentration values after fasting, and in the glucose tolerance test, were within the expected range for mammals. We postulate that this group of rodents has compensatory traits that may permit the maintenance of standard values of plasma glucose.

Animals↗
PubMed2005

From rodent reagents to human therapeutics using antibody guided selection.

Guided selection is a method of producing a human version of a rodent or any other non-human antibody. The process is a serial transition from rodent to human via rodent-human chimaerics, through to a panel of human antibodies with similar characteristics to those of the starting rodent antibody. The guided selection process can be undertaken using either phage display or ribosome display, and chimaeric antibodies can be made either in series or parallel, with or without the retention of the original rodent CDR3s. Guided selection has successfully been used for the generation of a number of human versions of rodent antibodies, including HUMIRA, an inhibitor of tumour necrosis factor-alpha which is approved for the treatment of moderate to severe rheumatoid arthritis in over 40 countries.

Adalimumab↗
PubMed2001

The role of neurosteroids and non-genomic effects of progestins and androgens in mediating sexual receptivity of rodents.

Progestins and androgens modulate sexual receptivity in rodents, in part through mechanisms independent of traditional intracellular steroid receptors. Progesterone (PROG) in the ventromedial hypothalamus (VMH) and ventral tegmental (VTA) facilitates lordosis but has different actions in these brain areas. Primarily using lordosis in rodents as an in vivo experimental model, we have examined the effects that progestins exert in the midbrain and hypothalamus. Localization and blocker studies indicate that PROG's actions in the VMH require intracellular progestin receptors (PRs) but in the VTA they do not. Progestins that have rapid, membrane effects, and/or are devoid of affinity for PRs, facilitate lordosis when applied to the VTA. Manipulation of GABA and/or GABA(A)/benzodiazepine receptor complexes (GBRs) in the VTA alters lordosis, which suggests that progestins may interact with GBRs to facilitate receptivity by enhancing the function of GABAergic neurons. Interfering with PROG's metabolism to, or the biosynthesis of, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG or allopregnanolone), the most effective endogenous GBR agonist, in the VTA attenuates female sexual behavior in rodents. Stimulation of mitochondrial benzodiazepine receptors (MBRs), which enhances neurosteroid production, by infusions of an MBR agonist to the VTA enhances lordosis. 3alpha,5alpha-TH PROG is increased in the midbrain of mated>proestrous>diestrous rodents. These data suggest that in the VTA, PROG may facilitate lordosis following metabolism to and/or biosynthesis of 3alpha,5alpha-TH PROG, which may have subsequent actions at GBRs and/or MBRs to acutely modulate female sexual behavior in rodents. The 3alpha-hydroxysteroid oxidoreduced metabolite of dihydrotestosterone (DHT), 5alpha-androstane-3alpha,17beta-diol (3alpha-androstanediol), is important for termination of sexual receptivity in rodents and has these effects in the absence of functional intracellular androgens receptors. As well, altering GBR function in the hypothalamus can influence 3alpha-androstanediol's inhibition of sexual receptivity. Through actions in the hypothalamus that are independent of intracellular androgen receptors but involving GBRs, 3alpha-androstanediol inhibits lordosis. These findings suggest that the PROG metabolite and pregnane neurosteroid, 3alpha,5alpha-TH PROG, and the testosterone metabolite and androstane neurosteroid, 3alpha-androstanediol, can have proximate influences on lordosis that is via nonclassical actions at intracellular steroid receptors.

Androgens↗
PubMed1998

Cytochrome P450 induction in feral Cricetid rodents: a review of field and laboratory investigations.

The constitutive and inducible hepatic cytochromes P450 of various feral Cricetid rodents (family Cricetidae, comprising various New World rats and mice, hamsters, gerbils and voles), have been examined in a relatively limited number of field and laboratory investigations. These studies, reviewed herein, have employed substrates and immunochemical reagents that are diagnostic for individual P450 subfamilies of Rattus norvegicus (the common laboratory species derived from the Norway rat, a member of the family Muridae). The results have demonstrated that the feral rodents display hepatic responses to prototypic CYP1A inducers (3-methylcholanthrene, beta-naphthoflavone) similar to those displayed by R. norvegicus and Mus musculus (the common laboratory species derived from the house mouse, another member of the family Muridae). At least one study has demonstrated the induction, by ethanol, of a protein immunochemically similar to CYP2E1 in a Cricetid rodent. In Cricetid rodents, phenobarbital-type inducers cause the induction of a hepatic protein immunologically similar to that primarily induced (CYP2B) in R. norvegicus and M. musculus. The proteins induced in the Cricetid rodents, however, exhibit striking differences in substrate specificity, compared to the proteins induced in R. norvegicus. These results indicate that the previously described differences between the P450 induction responses exhibited by the commonly utilized laboratory species R. norvegicus and M. musculus (family Muridae) and the Syrian hamster and gerbil (family Cricetidae) are observed as a generality for members of the Cricetid family of rodents.

Animals↗
PubMedDate not supplied

Methods determining phosphor imaging limits of quantitation in whole-body autoradiography rodent tissue distribution studies affect predictions of 14C human dosimetry.

INTRODUCTION: Radioluminography, or phosphor imaging, is often used in rodent quantitative whole-body autoradiography (QWBA) studies to determine the tissue distribution and pharmacokinetic (PK) parameters of new pharmaceutical entities in rodents. The rodent tissue pharmacokinetics information are then used to predict human radiation exposure to 14C or 3H during human radioisotope mass balance studies. The human dosimetry estimation can be biased by the method used to determine the lower limit of quantitation (LOQ) of the phosphor imager. A survey of autoradiographers revealed that at least five different methods are used to determine phosphor imager LOQ. The objective of this study is to compare and evaluate the human dosimetry estimates obtained by applying those five LOQ methods to a single set of WBA data. METHODS: Five different phosphor imager LOQ determination methods were applied to a single set of QWBA rodent tissue distribution data to produce five tissue concentration time profiles. Tissue PK parameters were determined for each profile and subsequently used to calculate the 14C exposure for a proposed human 14C mass balance study. RESULTS: A threefold difference was observed among the five predictions of human 14C exposure when the five different phosphor imager LOQ values were applied to the initial data set. DISCUSSION: The method chosen to determine the phosphor imaging LOQ for QWBA rodent tissue distribution study could impact the human 14C exposure estimates. The end result may either under- or overestimate the 14C-tissue exposure in humans during radioisotope studies, depending on the method used to determine LOQ. We recommend two approaches to reduce the variations in the determination of rodent tissue distribution pharmacokinetics: (1) Set more sampling time points to cover the terminal phase to obtain more accurate t 1/2 and (2) use Method 3 or the small sized sampling tool of Method 5 for LOQ determinations because it is a balanced approach for both simplicity and accuracy.

Animals↗