Prediction of auditory brain stem responses damage in patients with head-and-neck cancers receiving radiotherapy using the functional assays of normal tissue complication probability models.

AIM: The purpose of this study was to set four NTCP models on clinical data and develop a model that calculates the possibility of hearing damage due to irradiation of healthy and at-risk brainstem tissue. MATERIALS AND METHODS: ABR tests were performed on 50 head-and-neck cancer patients three years after radiotherapy for evaluation of lesions in a part of the auditory nerve or the auditory pathway in the brainstem. RESULTS: It indicated a significant difference in the latency of the waves assessed by the ABR test between the two groups. The paired sample t-test indicated the latency time of waves I, III, V, I-III, and I-V (P < 0.001) in the right ear, and in the left ear latency time of waves III, V, I-III, I-V, and III-V (P < 0.001) were significantly higher in the case group's ear than those in the control group. The confidence interval of the fitted parameters was 95% for NTCP models. ABR test's binary outcome with differential dose-volume histograms (dDVHs) was calculated and imported as input to the NTCP modeling. The values of the parameters n = 2.3-2.9 and the value s = 1 were obtained, which indicated that the brainstem organ is seriality. CONCLUSION: The best model ranked for the prediction of brainstem hearing damage was the logit model, which had the lowest Akaike value. The nervousness of the auditory organ of the brainstem (VIII nerve) can be declared as one of the reasons for being independent of the received dose.

Omega-3 fatty acids and health of auditory and vestibular systems: a comprehensive review.

PURPOSE: The purpose of this study was to comprehensively review animal and human studies that explore the role of omega-3 PUFAs in maintaining the health of the auditory organ across all life stages. METHODS: This narrative review involved searching Scopus, PubMed, Google Scholar, and Cochrane Library databases for relevant articles from December 1980 to July 2023. RESULTS: some animal and human studies suggest that both deficiency and excessive intake of long-chain omega-3 PUFAs, particularly docosahexaenoic acid (DHA), can lead to auditory neural conduction impairment and reduced hearing acuity from fetal development to old age (presbycusis). These effects are likely to be dependent on the dosage. Some research indicates that an excessive intake of omega-3, rather than a deficiency, can result in nutritional toxicity and hearing impairments. Animal studies highlight the positive impact of omega-3 supplements with high DHA content in addressing hearing damage, but human research on this subject is limited. Furthermore, certain studies propose that omega-3 PUFAs may prevent or delay age-related hearing loss, with high plasma omega-3 concentration, particularly long-chain omega-3 PUFA, linked to reduced hearing loss. Additionally, consuming fish more than twice a week may be associated with a lower risk of hearing loss in adulthood, with these effects potentially influenced by age and gender. However, the majority of studies have been conducted on animals, and clinical trials are scarce. Research on the influence of omega-3 PUFAs on the peripheral and central vestibular systems remains limited. CONCLUSION: This article delves into the impact of omega-3 on the auditory-vestibular system, exploring its influence on neurodevelopment, protection, and treatment. It not only highlights specific research gaps but also offers valuable insights for potential future studies.

The Prevalence of Central Auditory Processing Disorder in Elementary School Students of Kerman, Iran.

Objectives: This study aimed to determine the prevalence of central auditory processing disorder (CAPD) in elementary school students in Kerman, Iran, during 2018-2019. Materials & Methods: This cross-sectional study was conducted on 1369 elementary school students in Kerman. These students were selected by cluster sampling from different areas of Kerman and then screened using the Buffalo Model Questionnaire (BMQ). Based on the data obtained from the questionnaire, normal children were excluded from the study. Then, children with suspected central auditory processing disorder (CAPD) underwent ear exams and were excluded from the study in case of abnormal results in the tympanic membrane examination (rapture-effusion). The remaining subjects underwent peripheral audiometry evaluation, and children with abnormal audiometry were excluded from the study. Finally, the remaining children with suspicious screening results, a normal examination, and normal audiometry underwent a specific test to detect Central auditory processing disorder. Data analysis was carried out using SPSS software. Results: One thousand three hundred sixty-nine primary school students with a mean age of 9.15 ±2.63 years enrolled in this study. 52%% of students were male. 8.03% of them had CAPD. A statistically significant relationship was found between the prevalence of CAPD and gender (P<0.001), place of residence (P<0.001), history of middle ear inflammation (P<0.001) and history of head injury. Conclusion: The quality of life of these students with CAPD can be improved via timely recognition of CAPD and the provision of appropriate preventive and therapeutic facilities.

A machine learning approach for prediction of auditory brain stem response in patients after head-and-neck radiation therapy.

Objective: The present study aimed to assess machine learning (ML) models according to radiomic features to predict ototoxicity using auditory brain stem responses (ABRs) in patients with radiation therapy (RT) for head-and-neck cancers. Materials and Methods: The ABR test was performed on 50 patients having head-and-neck RT. Radiomic features were extracted from the brain stem in computed tomography images to generate a radiomic signature. Moreover, accuracy, sensitivity, specificity, the area under the curve, and mean cross-validation were used to evaluate six different ML models. Results: Out of 50 patients, 21 participants experienced ototoxicity. Furthermore, 140 radiomic features were extracted from the segmented area. Among the six ML models, the Random Forest method with 77% accuracy provided the best result. Conclusion: According to the ML approach, we showed the relatively high prediction power of the radiomic features in radiation-induced ototoxicity. To better predict the outcomes, future studies on a larger number of participants are recommended.

Does insular cortex lesion cause tinnitus in rats?

Objectives: Tinnitus is defined as ringing of the ears that is experienced when there is no external sound source, and is an auditory phantom sensation. The insula as a multimodal cortex has been shown to be involved in the processing of auditory stimuli rather than other sensory and motor processing and reported to correlate with some aspects of tinnitus. However, its exact role is not clear. The present study aimed to investigate the effect of excitotoxic lesions limited to the insular cortex on the ability to detect a gap in background noise. Materials and Methods: Gap detection test and prepulse inhibition, two objective measurements of auditory startle response, were measured, in 33 male Wistar rats, before and up to four weeks after insular lesion in three experimental groups (sham, control, and lesion). Results: The ability to detect the gap interposed between 60 db background noise was impaired at weeks 2, 3, and 4 following insular lesion, while prepulse inhibition remained intact up to four weeks after surgery. Conclusion: These findings indicated that excitotoxic lesions of the insular cortex may produce a tinnitus-like phenomenon in rats while sparing the hearing sensitivity; suggesting that the insular cortex may have a role in the development of tinnitus.

Comparison of Maturity in Auditory-Visual Multisensory Processes With Sound-Induced Flash Illusion Test in Children and Adults.

Multi-sensory neural pathways of auditory-visual maturation develop before birth in humans. Maturation levels of multi-sensory brain pathways are very different in children in comparison to adults. Auditory sensory neural maturation occurs earlier than visual sensory neural maturation. Auditory-visual multi-sensory processing can assess using objective (event-related potential tests) and subjective (behavioral tests). In this study, we use the sound-induced flash illusion (SIFI) test as a subjective test. The results of the SIFI test show that when the test is complex, the younger children performed not as accurately as the older ones. This difference occurs due to the complexity in the auditory-visual multi-sensory pathway maturation. Therefore, it is necessary to evaluate and analyze the results of different age groups with their normative data.

A comprehensive review of the effects of caffeine on the auditory and vestibular systems.

Coffee, of which caffeine is a critical component, is probably the most frequently used psychoactive stimulant in the world. The effects of caffeine on the auditory and vestibular system have been investigated under normal and pathological conditions, such as acoustic trauma, ototoxicity, auditory neuropathy, and vestibular disorders, using various tests. Lower incidences of hearing loss and tinnitus have been reported in coffee consumers. The stimulatory effect of caffeine is represented by either a shorter latency or enhanced amplitude in electrophysiological tests of the auditory system. Furthermore, in the vestibular system, oculomotor testing revealed significant effects of caffeine, while other tests did not reveal any significant caffeine effects. It could be that caffeine improves transmission in the auditory and vestibular systems' central pathways. Importantly, the effects of caffeine seem to be dose-dependent. Also, inconsistent findings have been observed regarding caffeine's effects on the auditory and vestibular systems and related disorders. Overall, these findings suggest that caffeine does not strongly influence the peripheral auditory and vestibular systems. Instead, caffeine's effects seem to occur almost solely at the level of the central nervous system.

Can Pitch Mismatch Be Diagnosed in Children Who Use Electric-Acoustic Stimulation?

Introduction Pitch mismatch is one of the most important problems of users of bimodal cochlear implants, which affects their life satisfaction. Children with acquired hearing loss cannot explain their pitch mismatch problems, as they have had no auditory experience. This study tries to diagnose pitch mismatch in these children through the sound-induced flash illusion test. Materials and methods In this study, 20 children with a bimodal cochlear implant and 20 children with normal hearing, within the age range of 8 to 13 years old, were examined using the sound-induced flash illusion test. In this test, participants received one flash with one to four beep sounds, and they were asked to indicate the number of perceived flashes. Results The results revealed that in the bimodal implantation group, when the flash was provided with one beep, at certain frequencies, children expressed that they saw two flashes. However, the results were not the same in children with normal hearing. Conclusion The results indicated that at frequencies where the auditory information of the hearing aids and those of the cochlear implants overlap, pitch mismatch develops, which can significantly affect the auditory performance of bimodal users.

Comparison of radiation and chemoradiation-induced sensorineural hearing loss in head and neck cancer patients.

AIM: The purpose of this study was to assess and compare the incidence and severity of sensorineural hearing loss (SNHL) in head-and-neck patients undergoing radiotherapy (RT) and concurrent cisplatin-based chemoradiotherapy (CRT). MATERIALS AND METHODS: Pure tone audiometry (PTA) was performed at 0.25-12 kHz on 35 RT and 25 CRT patients after 12-month followed up. The hearing loss was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria. RESULTS: SNHL increased to 84% in patients who had received CRT, compared with 26% increasing in patients who had treated with RT. There was an increased risk of SNHL at all frequencies for ears received a cochlear mean dose >50 Gy in RT group, compared to those receiving cochlear mean dose >30 Gy in CRT group. SNHL was more severe at higher frequencies in both patient groups. CONCLUSION: Characteristic of radiation-induced SNHL is different from CRT-induced SNHL, especially in threshold radiation dose and PTA frequency.

Investigating the Effects of Hearing Loss and Hearing Aid Digital Delay on Sound-Induced Flash Illusion.

BACKGROUND AND OBJECTIVES: The integration of auditory-visual speech information improves speech perception; however, if the auditory system input is disrupted due to hearing loss, auditory and visual inputs cannot be fully integrated. Additionally, temporal coincidence of auditory and visual input is a significantly important factor in integrating the input of these two senses. Time delayed acoustic pathway caused by the signal passing through digital signal processing. Therefore, this study aimed to investigate the effects of hearing loss and hearing aid digital delay circuit on sound-induced flash illusion. SUBJECTS AND METHODS: A total of 13 adults with normal hearing, 13 with mild to moderate hearing loss, and 13 with moderate to severe hearing loss were enrolled in this study. Subsequently, the sound-induced flash illusion test was conducted, and the results were analyzed. RESULTS: The results showed that hearing aid digital delay and hearing loss had no detrimental effect on sound-induced flash illusion. CONCLUSIONS: Transmission velocity and neural transduction rate of the auditory inputs decreased in patients with hearing loss. Hence, the integrating auditory and visual sensory cannot be combined completely. Although the transmission rate of the auditory sense input was approximately normal when the hearing aid was prescribed. Thus, it can be concluded that the processing delay in the hearing aid circuit is insufficient to disrupt the integration of auditory and visual information.

The effect of insular cortex lesion on hyperacusis-like behavior in rats.

Background and objectives: Hyperacusis is hypersensitivity and extreme response to the intensity of sound that is tolerable in normal subjects. The mechanisms underlying hyperacusis has not been well understood, specially the role of insular cortex. The aim of this study is to investigate the role of insular cortex in hyperacusis like behavior. Material and methods: The number of 33 male wistar rats weighting 170-250 gr were allocated randomly in three groups; control, sham, and insular lesion. Auditory startle responses (ASR) to different intensities of stimuli (70, 80, 90, 100, and110 dB without background noise as well as 110 dB in the presence of 70, 80 dB background noise) were measured before and up to four weeks after intervention. Results: Data analyses showed an increase in ASR to 100 dB stimulus without background noise one week after insular lesion, and increased responses to other intensities two weeks after lesion. Furthermore, there was a decrease in ASR to 110 dB stimulus with 80 dB background noise two weeks after insular lesion. However, no significant difference was observed in 70 dB background noise. The changes in ASR lasts at least four weeks.Conclusion: The findings indicated that there was an increase in ASR in the absence of background noise following cortical excititoxic lesion limited to insular cortex, while there was a decrease in responses in the presence of background noise which suggests possible increased sensitivity to sound loudness as a hyperacusis-like phenomenon. The study showed a significant relationship between insular cortex lesion and ASR in rats.

Effects of Caffeine on Auditory- and Vestibular-Evoked Potentials in Healthy Individuals: A Double-Blind Placebo-Controlled Study.

BACKGROUND AND OBJECTIVES: The blockage of adenosine receptors by caffeine changes the levels of neurotransmitters. These receptors are present in all parts of the body, including the auditory and vestibular systems. This study aimed to evaluate the effect of caffeine on evoked potentials using auditory brainstem responses (ABRs) and cervical vestibular-evoked myogenic potentials (cVEMPs) in a double-blind placebo-controlled study. SUBJECTS AND METHODS: Forty individuals (20 females and 20 males; aged 18-25 years) were randomly assigned to two groups: the test group (consuming 3 mg/kg pure caffeine powder with little sugar and dry milk in 100 mL of water), and the placebo group (consuming only sugar and dry milk in 100 mL water as placebo). The cVEMPs and ABRs were recorded before and after caffeine or placebo intake. RESULTS: A significant difference was observed in the absolute latencies of I and III (p<0.010), and V (p<0.001) and in the inter-peak latencies of III-V and I-V (p<0.001) of ABRs wave. In contrast, no significant difference was found in cVEMP parameters (P13 and N23 latency, threshold, P13-N23 amplitude, and amplitude ratio). The mean amplitudes of P13-N23 showed an increase after caffeine ingestion. However, this was not significant compared with the placebo group (p>0.050). CONCLUSIONS: It seems that the extent of caffeine's effects varies for differently evoked potentials. Latency reduction in ABRs indicates that caffeine improves transmission in the central brain auditory pathways. However, different effects of caffeine on auditory- and vestibular-evoked potentials could be attributed to the differences in sensitivities of the ABR and cVEMP tests.

Short-term impacts of biochar, tillage practices, and irrigation systems on nitrate and phosphorus concentrations in subsurface drainage water.

Leaching of nitrogen (N) and phosphorus (P) from agricultural lands can cause serious environmental problems such as eutrophication. The objective of this study was to investigate the impacts of biochar application, tillage practices, and irrigation systems on nitrate and dissolved phosphorus (DP) concentrations in subsurface drainage water and grain yield of winter wheat using a strip-split plot design with 3 replications. Irrigation at three different levels (flood (Ifl), furrow (Ifu), and sprinkler (Is) systems) considered as main factor, tillage at two levels (reduced tillage (Tr) and conventional systems (Tc)) as subplot factor, and bagasse biochar at two levels (without biochar (B0) and 20 ton ha-1 biochar (B1)) as sub-subplot factor. Polyvinyl chloride (PVC) standpipes were used in each sub-subplot to collect leachate water at 100-cm depth. The results indicated that irrigation had significant effects on yield, collected water volume (CWV), nitrate, and DP concentrations (P < 0.01). Interaction of tillage and irrigation was significant for grain yield (P < 0.05). Biochar application only caused a significant decrease in nitrate concentration under sprinkler irrigation (P < 0.05), while no significant impact was observed under flood and furrow irrigation systems. Under sprinkler irrigation, the total nitrate collected in the PVC standpipes decreased by 37.51 and 34.29% compared with flood and furrow irrigations, respectively. Biochar application reduced the total nitrate collected by 16.84%, while difference among tillage treatments was negligible (4.51%). The total DP collected under sprinkler irrigation was lower in comparison with flood and furrow irrigations by 42.24 and 38.76%, respectively. Biochar application reduced the total DP collected by 10.84%, while reduced tillage increased the total DP collected by 8.90% compared with the conventional tillage.

Protective Effects of Silymarin Against Age-Related Hearing Loss in an Aging Rat Model.

Age-related hearing loss (ARHL) is one of the most common chronic degenerative disorders. Several studies have indicated that supplementation with some antioxidants can slow down the progression of ARHL. Despite several lines of evidence about the potent antioxidant and anti-aging effects of silymarin, its protective effect against ARHL has not evaluated yet. The aim of the current study was to investigate the effects of silymarin in prevention of ARHL in a d-Galactose-induced aging rat model for the first time. 45 male wistar rats aged 3-month old were divided into 5 groups: group 1, 2 and 3 received 500 mg/kg/day d-Gal plus 100, 200 and 300 mg/kg/day silymarin respectively for 8 weeks, placebo group received 500 mg/kg/day d-Gal plus propylene glycol as placebo, and control group received normal saline during this period of time. Auditory brainstem responses were measured at several frequencies (4, 6, 8, 12 and 16 kHz) before and after the intervention. Placebo group and group 3 showed significant ABR threshold increase across frequencies of 4, 6, 16 kHz compared with the other groups (P < 0.05). However, rats treated with silymarin 100 and 200 mg/kg/day plus d-Gal did not show any significant ABR threshold shifts. Similarly, ABR amplitude of P2 at 4, 8 kHz and P1, P4 at 4 kHz in the placebo group and group 3 were decreased significantly compared with other groups (P < 0.05). However, no significant differences are found in ABR absolute and inter-peak latencies between groups (P > 0.05). The findings indicates that silymarin with doses of 100 and 200 mg/kg/day has protective effect against ARHL and it can be supplemented into the diet of older people to slow down the progression of age-related hearing loss.

Validity of correction factors applied to auditory steady-state responses (ASSRs) in normal hearing adults in chartr EP system.

OBJECTIVES: Even though many patients undergoing auditory steady-state response (ASSR) testing have some degree of hearing loss, some have normal hearing and ASSR often overestimates the behavioral thresholds in this group. In most commercial ASSR systems such as Chartr EP, a default correction factor is applied to compensate for this difference. Little is known, however, as how the correction factor compensates for the difference between ASSR and pure tone audiometry (PTA) thresholds as a function of carrier or modulation frequency (MF) in a commercial ASSR system. Our goal is to evaluate this relationship. METHODS: Twenty-four normal hearing adults were examined for both PTA and ASSR (Chartr EP system, GN Otometrics). ASSR thresholds were obtained at three MFs (20, 40, and 80 Hz). The difference scores were obtained by subtracting PTA from ASSR thresholds at each frequency for each subject. The corrected ASSR thresholds, then, were compared with the PTA thresholds across MFs and carrier frequencies. RESULTS: The default correction factors in the ASSR equipment differed significantly from the difference scores at all MFs and carrier frequencies (n = 24, p < 0.005). The correlation between corrected ASSR and PTA thresholds at most MFs and carrier frequencies were medium to poor. CONCLUSIONS: At most MFs and carrier frequencies, the default correction factors defined by the manufacturer do not compensate for the difference between ASSR and PTA thresholds in normal hearing adults. The use of the default correction factors in Chartr EP system for the normal hearing adults needs special considerations.

Does 5, 7-Dihydroxytryptamine injection into nucleus accumbens cause hyperacusis?

Hyperacusis may be defined as diminishing tolerance to moderate and high intensity sounds in people with normal hearing sensitivity. Serotonin plays a critical role in some of auditory tasks including startle reflex and prepulse inhibition. Serotonin deficiency can cause some diseases which can coincide with hyperacusis. The aim of the present study was to investigate the probable influence of serotonergic depletion in nucleus accumbens (NAcc) on the startle reflex. The startle reflexes were examined in Wistar rats (n: 48) in different intensities with and without the background noise. The amplitude of startle reflex significantly increased in NAcc-injected rats without background noise, while this difference disappeared in the presence of background noise in all intensities. These data proposed that the injection of 5, 7-Dihydroxytryptamine (5, 7-DHT) into nucleus accumbens will cause hyperacusis-like behavior, and strengthens the possibility of the role of serotonin and nucleus accumbens in hyperacusis.

Normal tissue complication probability modeling of radiation-induced sensorineural hearing loss after head-and-neck radiation therapy.

PURPOSE: The aim of this study was to generate the dose-response curves by six normal tissue complication probability (NTCP) models and ranking the models for prediction of radiation induced sensorineural hearing loss (SNHL) caused by head and neck radiation therapy (RT). MATERIALS AND METHODS: Pure tone audiometry (PTA) was performed on 70 ears of patients for 12 months after the completion of RT. The SNHL was defined as a threshold shift ≤15 dB at two contiguous frequencies according to the common toxicity criteria for adverse events scoring system. The models evaluated were: Lyman and Logit; Mean Dose; relative seriality (RS); Individual critical volume (CV); and population CV models. Maximum likelihood analysis was used to fit the models to experimental data. The appropriateness of the fit was determined by the two-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. RESULTS: The dose of 50% complication rate (D50) was 51-60 Gy. Three of the examined models fitted well with clinical data in a 95% confidence interval. The RS model was ranked as the best model of prediction for radiation induced SNHL. CONCLUSIONS: Cochlea shows a different behavior against different NTCP models; it may be due to its small size.

Vestibulo-Ocular Reflex Abnormalities in Posterior Semicircular Canal Benign Paroxysmal Positional Vertigo: A Pilot Study.

INTRODUCTION: Benign paroxysmal positional vertigo (BPPV), involving the semicircular canals, is one of the most common diseases of the inner ear. The video head impulse test (vHIT) is a new test that examines the function of the canals. This study aimed to investigate the vestibulo-ocular reflex (VOR) gain, gain asymmetry and saccades after stimulating all six canals in patients definitively diagnosed with posterior semicircular canal BPPV (PSC-BPPV). MATERIALS AND METHODS: Twenty-nine unilateral PSC-BPPV patients with normal oculographic and caloric results were enrolled in this study. vHIT was performed on six canals, and VOR gain, gain asymmetry and saccades were measured. RESULTS: Sixteen (55.17%) patients had abnormal posterior canal VOR gains in the ipsilesional ear. VOR gains in both horizontal canals were within normal limits. Superior canal VOR gains were mostly lower than normal and were not correlated to PSC abnormalities (P>0.05). No corrective saccades could be observed. CONCLUSION: VOR gain in the direction of the posterior semicircular canal may be reduced in PSC-BPPV patients. Evaluation of PSC-VOR parameters could be beneficial, although superior canal measurements should be interpreted with caution.

Life cycle environmental impacts of bioethanol production from sugarcane molasses in Iran.

In recent years, bioethanol from sugarcane molasses has been produced on an industrial scale in Iran. The aim of this study was to evaluate molasses-based bioethanol production from an environmental point of view. Data were collected from Debel Khazai agro-industry situated in southern region of Iran by using face-to-face interviews and annual statistics of 2010 to 2016 (6-year life cycle of sugarcane cultivation). Ten impact categories including abiotic depletion (AD), acidification (AC), eutrophication (EP), global warming potential (GWP), ozone layer depletion (OLD), human toxicity (HT), freshwater aquatic ecotoxicity (FE), marine aquatic ecotoxicity (ME), terrestrial ecotoxicity (TE), and photochemical oxidation (PO) were selected based on CML methodology. Inventory data for production of the inputs were taken from Ecoinvent, BUWAL 250, and IDMAT 2001 databases. The results revealed that in sugarcane cultivation process, electricity and trash burning were the most important contributors to all impact categories except OLD and TE. In industrial phase, natural gas had the highest contribution to the most impact categories. Greenhouse gas (GHG) emission for production of 1000 L molasses-based bioethanol was 1322.78 kg CO2 eq. By comparing total GHG emissions from 1000 L bioethanol to gasoline, the net avoided GHG emissions came out at 503.17 kg CO2 eq. According to results, it is clear that with increasing irrigation efficiency and improving performance of heating systems in industrial phase, environmental burdens would be significantly reduced.

Life cycle environmental impacts of saffron production in Iran.

Saffron is regarded as an important crop in Iranian agricultural economics that needs to be investigated to produce the environmentally friendlier product. In the present study, saffron production as an important agricultural production system in Iran was evaluated thoroughly from an environmental point of view. Data were collected from saffron farmers in Southern Khorasan province of the country with face-to-face questionnaire method during cropping period of 2013-2014. The system boundary was considered from the production of raw input materials to the harvested saffron. In order to identify the main hotspot during cultivation, impact categories were considered using CML methodology and cumulative exergy demand (CExD) indicator. Based on the results, chemical fertilizers N and P were the main hotspots in abiotic depletion (AD), acidification (AC), global warming (GWP), and photochemical oxidation (PO) impact categories, while diesel fuel was the main hotspot in fresh water aquatic ecotoxicity (FE), marine aquatic ecotoxicity (ME), and terrestrial ecotoxicity (TE). Direct emission from diesel fuel combustion (saffron) was the main hotspot only in human toxicity (HT). The small farms had the highest amounts of AD, AC, EP, GWP, and PO indicators in comparison with the medium and large farms. Total CExD indicator for production of 1 kg saffron was 1894.23 MJ eq. Totally, large farms (bigger than 1 ha) had better environmental performance considering all the impact categories.