scholarly journals Humidifier disinfectant, sodium dichloroisocyanurate (NaDCC): assessment of respiratory effects to protect workers’ health

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
DongSeok Seo ◽  
JiMin Jo
Keyword(s):  
Recovery Period ◽  
White Blood Cells ◽  
Inhalation Exposure ◽  
Test Substance ◽  
Upper Respiratory Tract ◽  
Substance Exposure ◽  
Adverse Effect Level ◽  
Sodium Dichloroisocyanurate ◽  
Effect Level ◽  
Males And Females

AbstractIn South Korea, it has been found that biocides used to control and eliminate harmful organisms are used as humidifier disinfectants and cause lung disease in users. Hence, efforts have been focused on studying the toxicity of biocides in workers who handle them. The purpose of this study was to evaluate the effects of inhalation exposure to sodium dichloroisocyanurate (NaDCC) to protect the health of workers handling NaDCC. F344 rats were exposed to 0.8-, 4-, and 20-mg/m3 of NaDCC for 6 h per day, 5 days per week for 14 days, and the recovery period after exposure was 14 days. In the 20-mg/m3-exposure group, we observed a decrease in food intake in females, a weight loss in males, and a decrease in partially active thromboplastin time in males and females 2 weeks after exposure. We noted a decrease in white blood cells in males in the 4- and 20-mg/m3-exposed groups. Both males and females in the 20-mg/m3 group and males in the 4-mg/m3 group showed irritation in the larynx related to test substance exposure. However, these findings were not observed in the recovery group. The main target organs affected by repeated 2-week inhalation exposure to NaDCC were the nasal cavity and larynx in the upper respiratory tract. The No Observed Adverse Effect Level (NOAEL) was considered to be 0.8 mg/m3 because effects related to NaDCC exposure were observed even at of 4 mg/m3, and these effects were found to be reversible.

scholarly journals Humidifier disinfectant, sodium dichloroisocyanurate (NaDCC): Assessment of respiratory effects to protect workers’ health

2021 ◽  
Author(s):  
DongSeok Seo ◽  
JiMin Jo
Keyword(s):  
Recovery Period ◽  
White Blood Cells ◽  
Inhalation Exposure ◽  
Test Substance ◽  
Upper Respiratory Tract ◽  
Substance Exposure ◽  
Adverse Effect Level ◽  
Sodium Dichloroisocyanurate ◽  
Effect Level ◽  
Males And Females

Abstract Biocides are used to control and remove all harmful organisms. In South Korea, they are used in humidifier disinfectants and have been found to cause lung disease in users. Hence, efforts have been focused on studying the toxicity of biocides in workers who handle them. The purpose of this study was to evaluate the effects of inhalation exposure to sodium dichloroisocyanurate (NaDCC) to protect the health of workers handling NaDCC. F344 rats were exposed to 0.8-, 4-, and 20-mg/m3 of NaDCC for 6 hours per day, 5 days per week for 14 days, and the recovery period after exposure was 14 days.In the 20-mg/m3 exposure group, we observed a decrease in food intake in females, a weight loss in males, and a decrease in partially active thromboplastin time in males and females 2 weeks after exposure. We noted a decrease in white blood cells in males in the 4- and 20-mg/m3 exposed groups. Both males and females in the 20-mg/m3 group and males in the 4-mg/m3 group showed irritation in the larynx related to test substance exposure. However, these findings were not observed in the recovery group. The main target organs affected by repeated 2-week inhalation exposure to NaDCC were the nasal cavity and larynx in the upper respiratory tract. The No Observed Adverse Effect Level (NOAEL) was considered to be 0.8 mg/m3 because the effects related to exposure of NaDCC were observed even at of 4 mg/m3. In addition, these effects were found to be reversible.

scholarly journals Humidifier Disinfectant, Sodium Dichloroisocyanurate (NaDCC): Assessment of Respiratory Effects to Protect Workers’ Health

2021 ◽  
Author(s):  
Dong Seok Seo ◽  
JiMin Jo
Keyword(s):  
Recovery Period ◽  
White Blood Cells ◽  
Inhalation Exposure ◽  
Test Substance ◽  
Upper Respiratory Tract ◽  
Substance Exposure ◽  
Target Organs ◽  
Adverse Effect Level ◽  
Sodium Dichloroisocyanurate ◽  
Effect Level

Abstract Background: Biocides are used to control and remove all harmful organisms. In South Korea, they are used in humidifier disinfectants and have been found to cause lung disease in users. Hence, efforts have been focused on studying the toxicity of biocides in workers who handle them. The purpose of this study was to evaluate the effects of inhalation exposure to sodium dichloroisocyanurate (NaDCC) to protect the health of workers handling NaDCC.Methods: F344 rats were exposed to 0.8-, 4-, and 20-mg/m3 of NaDCC for 6 h a day, 5 days a week for 14 days; the post-exposure recovery period was 14 days.Results: In the 20-mg/m3-exposure group, we observed a decrease in food intake in females, a weight loss in males, and a decrease in partially active thromboplastin time in males and females 2 weeks after exposure. We noted a decrease in white blood cells in males in the 4- and 20-mg/m3-exposed groups. Both males and animals in the 20-mg/m3 group and males in the 4-mg/m3 group showed irritation in the larynx related to test substance exposure. However, these findings were not observed in the recovery group.Conclusion: The main target organs affected by repeated 2-week inhalation exposure to NaDCC were the nasal cavity and larynx in the upper respiratory tract. The No Observed Adverse Effect Level (NOAEL) was considered to be 0.8 mg/m3 because the effects related to exposure of NaDCC were observed even at of 4 mg/m3. In addition, these effects were found to be reversible.

scholarly journals A 30-Day Preclinical Safety Evaluation Study of Recombinant Human Follicle-Stimulating Hormone in Female Rhesus Monkeys

2011 ◽  
Vol 30 (2) ◽  
pp. 153-161
Author(s):  
Yongming Cai ◽  
Zhengmin Chen ◽  
Zongpeng Zhang ◽  
Longsheng Zhang ◽  
Ming Li ◽  
...  
Keyword(s):  
Rhesus Monkeys ◽  
Follicle Stimulating Hormone ◽  
Recovery Period ◽  
Safety Evaluation ◽  
Evaluation Study ◽  
Chinese Origin ◽  
Female Rhesus ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Stimulating Hormone

The objective of this study was to identify potential target organs for toxicity of recombinant human follicle stimulating hormone (r-hFSH) in female rhesus monkeys and to establish a no observed adverse effect level (NOAEL). In all, 24 female rhesus monkeys (Chinese origin, weighing 3.4-5.2 kg, approximately 5 years of age) received repeated subcutaneous (sc) r-hFSH at doses of 10, 60, and 300 IU/kg per d or vehicle once daily for 30 days followed by a 15-day recovery period. Endometrial hyperplasia and dermal edema in the external genitals were found in some animals at 300 IU/kg per d. Pharmacologic-related multiple cystic follicles were found in all r-hFSH-treated groups. A weak, anti-FSH antibody response was detected at the end of treatment in animals administered 60 and 300 IU/kg per d. These results indicate that the primary effects of r-hFSH in female rhesus monkeys were related to its pharmacological activity on the reproductive system. The NOAEL was considered to be 60 IU/kg per d.

scholarly journals Clinical and Morphological Aspects in Assessing the Safety of OSPL-502 with Repeated Dose Administration

2018 ◽  
Vol 6 (9) ◽  
pp. 1581-1587
Author(s):  
Sergey A. Zhuchkov ◽  
Alexandr S. Kinzirsky ◽  
Irina V. Koroleva ◽  
Yuriy B. Vicharev
Keyword(s):  
Toxic Effect ◽  
Adrenal Glands ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Repeated Administration ◽  
Test Substance ◽  
Sprague Dawley ◽  
Adverse Effect Level ◽  
Pharmacological Substance ◽  
Effect Level

BACKGROUND: OSPL-502 is a new potential medicinal drug which stimulates a cognitive function. It is necessary to reveal clinical manifestations of its general toxic effect and determine organs that are most heavily affected by this pharmacological substance. AIMS: To describe and estimate clinical and histopathological changes in the organism of experimental animals in response to the repeated administration of pharmacological substance OSPL-502. MATERIAL AND METHODS: The study was conducted by the OECD Guidelines (Test No. 407) on Sprague-Dawley rats. The drug was administered at the dose of 20, 60 and 180 mg/kg. RESULTS: The repeated doses of OSPL-502 have not caused any toxic effects on the growth of body weight, food and water consumption of the tested animals, or affected the musculoskeletal system and exploratory behaviour of the rats in the doses of 20 and 60 mg/kg. The dose of 180 mg/kg (1800 times larger than the therapeutic dose) has shown clinical signs of toxicity in females but has not resulted in the death of the animals. Due to morphological methods, we have found histostructural changes in the liver, kidneys and adrenal glands of the rats that were treated with the test substance in the maximum dose. These changes are reversible and reduce within 14 days after the admission of the studied substances is cancelled. CONCLUSION: OSPL-502 at the dose of 180 mg/kg has a weakly pronounced toxic effect, the dose of 60 mg/kg is the threshold, and that of 20 mg/kg is no-observable-adverse-effect-level (NOAEL); the liver, kidneys and adrenal glands can be considered target-organs for the tested substance.

scholarly journals A 90-day toxicity and genotoxicity study with high-purity phenylcapsaicin

2018 ◽  
Vol 2 ◽  
pp. 239784731877306 ◽  
Author(s):  
Torbjørn Rage Paulsen ◽  
Sebastian Stiller ◽  
Klaus Weber ◽  
Claudia Donath ◽  
Gudrun Schreiband ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Clinical Chemistry ◽  
Human Lymphocytes ◽  
Recovery Period ◽  
Clinical Signs ◽  
Gene Mutations ◽  
Oral Gavage ◽  
Adverse Effect Level ◽  
Dose Oral ◽  
Effect Level

To evaluate the safety of the synthetic capsaicin analogue phenylcapsaicin (PheCap; 7-phenylhept-6-yne-acid-hydroxy-3-mathoxylbenzylamide, CAS no 848127-67-3), a 90-day repeated dose oral gavage of 0, 30, 100 or 250 mg/kg body weight (bw)/day toxicity study with a 28-day recovery period was conducted using Wistar rats. Examinations of clinical signs, body and organ weight, haematology, urinalysis, clinical chemistry, food consumption and macroscopic, as well as histopathological tissue examinations were carried out for signs of toxicity. Degenerative, but reversible changes in the liver at 250 mg/kg bw/day, and local irritating effects in the stomach at 100 and 250 mg/kg bw/day were found. These findings were associated with test item-related clinical symptoms, that is, diarrhoea, salivation and moving of bedding material. PheCap did neither cause gene mutations by base pair changes or frame shifts in the genome of the tester stains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 or TA 102 nor induce structural and/or numerical chromosomal damage in human lymphocytes. Therefore, it can be concluded that PheCap is not genotoxic. The No Observed Adverse Effect Level (NOAEL) of PheCap for systemic toxicity is considered to be at 100 mg/kg bw/day which is based on degenerative changes in the liver. Due to irritating effects in the stomach, the NOAEL for local effects was established at 30 mg/kg bw/day.

scholarly journals Looking for the LOAEL or NOAEL Concentration of Nickel-Oxide Nanoparticles in a Long-Term Inhalation Exposure of Rats

2021 ◽  
Vol 22 (1) ◽  
pp. 416
Author(s):  
Boris A. Katsnelson ◽  
Ivan N. Chernyshov ◽  
Svetlana N. Solovyeva ◽  
Ilzira A. Minigalieva ◽  
Vladimir B. Gurvich ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Nickel Oxide ◽  
Inhalation Exposure ◽  
Oxide Nanoparticles ◽  
Nickel Oxide Nanoparticles ◽  
Adverse Effect Level ◽  
Effect Level

Rats were exposed to nickel oxide nano-aerosol at a concentration of 2.4 ± 0.4 µg/m3 in a “nose only” inhalation setup for 4 h at a time, 5 times a week, during an overall period of 2 weeks to 6 months. Based on the majority of the effects assessed, this kind of exposure may be considered as close to LOAEL (lowest observed adverse effect level), or even to NOAEL (no observed adverse effect level). At the same time, the experiment revealed genotoxic and allergic effects as early as in the first weeks of exposure, suggesting that these effects may have no threshold at all.

Cis-1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz-Z) (2018)

2019 ◽  
Vol 35 (3) ◽  
pp. 180-188 ◽  
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Body Weight Gain ◽  
Inhalation Exposure ◽  
Individual Variability ◽  
Repeat Dose ◽  
Inhalation Study ◽  
Reduced Body ◽  
Adverse Effect Level ◽  
Effect Level

Cis-1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz-Z) is a clear, colorless liquid that finds uses as a foam-blowing agent, refrigerant, fire extinguishing agent, and solvent. HFO-1336mzz-Z is not an acute dermal or eye irritant and has very low acute toxicity via inhalation exposure (4-h lethal concentration (LC50) > 102,000 ppm). The no-observed adverse effect level (NOAEL) and lowest-observed adverse effect level (LOAEL) for cardiac sensitization (in epinephrine-challenged dogs) were 12,500 ppm and 25,000 ppm, respectively. In a GLP, subacute (4-week) repeat-dose inhalation study in Crl: CD(SD) male and female rats at exposure concentrations of 0, 2500, 5000, or 10,000 ppm, the only significant observations attributed to exposure were reduced body weight, reduced body weight gain, and reduced food consumption. The study NOAEL was determined to be 2500 ppm. Two separate GLP, 13-week repeat-dose inhalation studies (Organisation for Economic Cooperation and Development (OECD) 413) have been conducted on HFO-1336mzz-Z using male and female Crl: CD (SD) rats. In the first study, exposure concentrations were 0, 500, 1500, or 10,000 ppm, and in the second study, 0, 3000, 4000, 5000, or 7500 ppm. The only significant exposure-related observations in the first study were reductions in body weights, food consumption, and food efficiency in males and females at 10,000 ppm (study NOAEL = 1500 ppm). In the second study, done in part to better define the NOAEL, reductions in body weight and food consumption were observed in males at 7500 ppm; there were no exposure-related observations on these end points in females. Therefore, the study NOAEL was established at 5000 ppm for males and 7500 ppm for females. HFO-1336mzz-Z has also been examined for its potential to produce developmental toxicity in both Crl: CD(SD) rats (0, 500, 1500, or 10,000 ppm) and New Zealand White rabbits (0, 2500, 5000, 7500, or 15,000 ppm) according to GLP and OECD 414. The NOAEL for both maternal and fetal effects in rats was 1500 ppm and the NOAELs for maternal effects and fetal effects in rabbits were 5000 ppm and 7500 ppm, respectively. A non-GLP, two-generation reproductive pilot study, for a planned multigenerational study noted reduced body weight and body weight gain in males at 1500 ppm and above; the NOAEL for this pilot study was set at 500 ppm. There are no chronic toxicity/carcinogenicity studies available, and HFO-1336mzz-Z was not genotoxic/mutagenic in in vitro and in vivo studies. The NOAEL for male rats of 5000 ppm (based on reductions in body weight and food consumption) from the 13-week inhalation study was selected as the point of departure for the derivation of the 8-h time-weighted average (TWA), health-based workplace environmental exposure level (WEEL) value. This subchronic inhalation NOAEL was adjusted to account for duration of exposure, inter-individual variability, and intra-individual variability. The resulting 8-h TWA WEEL value of 500 ppm is fully expected to provide a significant margin of safety against the production of any potential adverse health effects in workers following long-term inhalation exposure to HFO-1336mzz-Z vapor.

scholarly journals Influence of Study Design on Developmental and Reproductive Toxicology Study Outcomes

2016 ◽  
Vol 45 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Paul M. D. Foster
Keyword(s):  
Adverse Effect ◽  
Statistical Power ◽  
Reproductive Tract ◽  
Reproductive Toxicity ◽  
Resolving Power ◽  
Subchronic Toxicity ◽  
Toxicology Study ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Males And Females

Regulatory studies of developmental and reproductive toxicity (DART) studies have remained largely unchanged for decades, with exposures occurring at various phases of the reproductive cycle and toxicity evaluations at different ages/times depending on the study purpose. The National Toxicology Program has conducted studies examining the power to detect adverse effects where there is a prenatal exposure, but evaluations occur postnatally. In these studies, examination is required of only 1 male and female pup from each litter beyond weaning. This provides poor resolving power to detect rare events (e.g., reproductive tract malformations). If an adverse effect is detected, there is little confidence in the shape of the dose–response curve (and the Benchmark Dose or No Observed Adverse Effect Level [NOAEL]). We have developed a new protocol to evaluate DART, the modified one generation study, with exposure commencing with pregnant animals and retention of 4 males and females from each litter beyond weaning to improve statistical power. These animals can be allocated to specific cohorts that examine subchronic toxicity, teratology, littering, and neurobehavioral toxicity in the same study. This approach also results in a reduction in animal numbers used, compared with individual stand-alone studies, and offers increased numbers of end points evaluated compared with recent Organization for Economic Cooperation and Development proposals.

A 90-Day Oral Gavage Toxicity Study of d-Methylphenidate and d, I-Methylphenidate in Beagle Dogs

2003 ◽  
Vol 22 (3) ◽  
pp. 215-226 ◽  
Author(s):  
Steve K. Teo ◽  
David I. Stirling ◽  
Steve D. Thomas ◽  
Mark G. Evans ◽  
Vikram D. Khetani
Keyword(s):  
Body Weight ◽  
Recovery Period ◽  
Clinical Pathology ◽  
Body Weight Loss ◽  
High Dose ◽  
Beagle Dogs ◽  
Weight Changes ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Therapeutic Doses

d-Methylphenidate ( d-MPH) was approved as a treatment for attention deficit hyperactivity disorder (ADHD) in children. The repeated-dose toxicity of the d enantiomer of d, l-methylphenidate ( d, l-MPH) was assessed in male and female Beagle dogs. Dogs were orally dosed twice a day in equally divided doses 6 hours apart for total daily doses of 1, 3, and 10 mg/kg/day d-MPH or 20 mg/kg/day d, l-MPH for 90 days, followed by a 30-day recovery period. The top d-MPH dose of 10 mg/kg was equimolar to 20 mg/kg d, l-MPH in d-MPH content. The 10-mg/kg d-MPH and d, l-MPH doses were at least 13 times the maximum therapeutic dose giving rise to systemic exposures that were equivalent to or at least 2 times greater than those at the maximum therapeutic doses in children. The 10-mg/kg d-MPH and 20-mg/kg d, l-MPH doses had systemic exposures that were equivalent to or two to five times greater than the maximum therapeutic plasma levels in children respectively. There was no treatment-related mortality in all doses tested. Reversible salivation, hyperactivity, and diarrhea were seen in the high-dose d-MPH and d, l-MPH groups. Significant body weight loss and reduction in food consumption were observed in males for both high-dose groups with weights comparable to control values by the end of the recovery period. There were no abnormal clinical pathology or macroscopic or microscopic findings. Based on body weight changes, the no-observed-adverse-effect level (NOAEL) of d-MPH in beagle dogs was 3 mg/kg/day.

scholarly journals Toxicity and Toxicokinetic Study of Subcutaneously Administered RPh201 in Minipigs

2018 ◽  
Vol 46 (6) ◽  
pp. 693-705 ◽  
Author(s):  
Yuval Ramot ◽  
Zadik Hazan ◽  
Andre Lucassen ◽  
Konstantin Adamsky ◽  
Vanessa Ross ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Recovery Period ◽  
Herbal Remedies ◽  
Drug Candidate ◽  
High Dose ◽  
Subcutaneous Injections ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Toxic Potential ◽  
Novel Drug

Mastic gum extracts are widely used as herbal remedies and are being tested for several clinical indications. Nevertheless, information on their safety is limited. RPh201 is an extract of the mastic gum, formulated and stabilized in a proprietary method, which is being developed as a novel drug candidate for neurological indications. The aim of this study was to assess the systemic toxic potential of RPh201, administered twice weekly by subcutaneous injections to minipigs, after 39 weeks of administration followed by a recovery period of 6 weeks. No clinical or dose-related signs were observed, but treatment-related findings were seen at the injection sites of the high-dose animals, composed of abscesses, chronic inflammation, and subcutaneous fibrosis. Abscesses >30 mm in size, graded as marked severity, were confined to the high-dose group and were considered as adverse. Minimal-slight subcutaneous and lymph nodes abscesses seen in control, low, and intermediate doses, related to the vehicle (cottonseed oil), were not considered as adverse. Additionally, minimal-to-slight cystic spaces or vacuolation related to the vehicle were observed in the skin, lymph nodes, kidney, and lungs. These findings were considered not to be adverse. The no-observed-adverse-effect level was considered to be 12.5 mg/kg/occasion.

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