• Toxicological Research
• /
• 제35권2호
• /
• pp.119-129
• /
• 2019

As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2'-hydroxy-5'-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

• Environmental Analysis Health and Toxicology
• /
• 제25권2호
• /
• pp.131-143
• /
• 2010

We performed the tests of acute and subchronic inhalation toxicity of methyl formate, which has limited toxicological data in spite of its widespread use and enhanced hazard consequent on its high volatility. The median lethal concentration ($LC_{50}$) was evaluated to be above 5,000ppm(12.27 mg/L). In the test with subchronic inhalation, there are no deaths, but with reduction of body weight, food intake, organ weight by exposure to 400 (0.98 mg/L) and 1,600 (3.92 mg/L) ppm, dose-dependently. There were statistical differences in some hematological and blood biochemical parameters as compared to control (e.g. neutrophile and lymphocyte in the 1,600 ppm group, calcium and A/G in 1,600 ppm group). Methyl formate under the exposure of 1,600 ppm showed the respiratory findings with nasal, it was confirmed that the chemical has respiratory hazard with 1,600 ppm inhalation exposure, induces nasal epithelial atrophy, olfactory cell degeneration/regeneration and the contraction of olfactory cells, etc. According to the notification with Ministry of Labor (No. 2009-68) for classification, labeling and MSDS of chemicals, it is suggested for methyl formate to be classified as category 4 in acute (10.0$4\leq20.0$ mg/L), category 2 (0.2$\leq$1.0 mg/L/6h, 90 days) in specific target organ-repeated exposure.

• 대한한의학회지
• /
• 제30권6호
• /
• pp.27-34
• /
• 2009

Objectives: To evaluate the acute toxic effects and approximate lethal dose of Cheonggan extracts (CGX) in SD rats and beagle dogs. Methods: Male and female rats were divided into 4 groups (Control, CGX 1250, CGX 2500, CGX 5000) respectively and male and female dogs were divided into two groups respectively (Control, CGX 5000) respectively. A single oral dose of CGX was treated to the rats and dogs. Mortality, signs of gross toxicity, and behavioral changes were observed over 14 days. All animals were observed every hour for 4 hours after administration and once a day thereafter for 14 days. Body weights were determined at $0_{th}$, $7_{th}$, and $14_{th}$ days. All surviving animals were sacrificed and necrotized. Major organs were inspected visually for gross findings. Results: No animals died in any of the groups during the experimental period (2 weeks), rats or dogs. Body weights of rats and dogs during the experiment continuously increased in all groups but there was no significant change. No abnormal clinical signs were observed for 2 weeks after a single administration of CGX in any dose group of CGX, rats or dogs. No abnormal findings in major organs were observed in any group of rats or dogs. Conclusion: CGX does not have acute toxic effects in rats or dogs. Therefore, an approximate lethal dose is assumed to exceed 5000 mg/kg in both rats and dogs.

• 한국환경과학회지
• /
• 제20권11호
• /
• pp.1383-1394
• /
• 2011

Environmental impacts of suspended solids (SS) released in coastal area by dredging, reclamation and construction can cause serious damages to coastal habitats and benthic organisms. Acute toxicity tests (4-7 days) were conducted to identify the relationship between SS concentration and mortality of three marine benthic species; benthic copepod (Tigriopus japonicus) adult, Pacific abalone (Haliotis discus hannai) spat, and olive flounder (Paralichthys olivaceus) fry. Benthic copepod was the most sensitive to SS followed by olive flounder fry and Pacific abalone spat, with an $LC_{50}$ (lethal concentration of 50% mortality) value of 61.0 mg/L and LOEC (lowest observed effective concentration) value of 31.3 mg/L for benthic copepod. LOEC and 7 day-$LC_{50}$ for Pacific abalone spat were 500.0 mg/L and 1887.7 mg/L, and those for olive flounder fry were 125.0 mg/L and 156.9 mg/L, respectively. The tolerance limits of the test species to SS revealed the various concentration ranges of SS, which reflects the physiology and ecology of the test species. These results are very valuable for the determination of SS concentration of effluents released into the coastal area by dredging, reclamation and construction etc. Also, sharp increase of SS can cause long-term damages to the benthic and sessile fauna by blanketing of benthic substratum. These experimental procedures for marine bioassay and acute toxicity results can be a useful guideline for practical management planning of SS discharge into coastal area.

• 한국환경보건학회지
• /
• 제47권2호
• /
• pp.166-174
• /
• 2021

Objectives: This study aimed to provide temporal Acute Exposure Guideline Levels (AEGL) for a hazardous substance as a pilot study. Methods: As one of the substances designated by the Korea Ministry of Environment as requiring preparations for potential accidents, formaldehyde was selected to estimate the AEGLs. The calculation was based on Haber's formula (Cn×t=k) using valid toxicity data (for humans/animals). A total of 96 points of AEGL levels were provided using an interval of five minutes over eight hours. Results: The AEGL-1 and 2 values were constant for the entire exposure duration at 0.9 ppm and 14 ppm, respectively. The values were obtained from clinical/animal tests, and the adaptation effect after a given exposure duration was also considered. AEGL-3 was based on animal toxicity data, and it was estimated from 127 ppm for the initial five minutes to 35 ppm for eight hours. Conclusions: More specific AEGL levels for formaldehyde could be obtained in this study using toxicity data with Haber's formula. Based on this methodology, it would be also possible to estimate AEGL levels that can be used at the scene of a chemical accident for other substances requiring preparation for potential accidents.

• 한국환경보건학회지
• /
• 제43권4호
• /
• pp.247-256
• /
• 2017

Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

• Environmental Engineering Research
• /
• 제12권1호
• /
• pp.16-20
• /
• 2007

Toxicity of metal plating wastewater was evaluated by using acute toxicity tests on Daphnia magna. To identify toxicants of metal plating wastewater, several manipulations such as solid phase extraction (SPE), ion exchange and graduated pH adjustment were used. The SPE test had no significant effect on baseline toxicity, suggesting absence of toxic non-polar organics in metal plating wastewater. However, anion exchange largely decreased the baseline toxicity by 88%, indicating the causative toxicants were inorganic anions. Considering high concentration of chromium in metal plating wastewater, it is thought the anion is Cr(VI) species. Graduated pH test showing independence of the toxicity on pH change strongly supports this assumption. However, as revealed by toxicity confirmation experiment, the initial toxicity of metal plating wastewater (24-h TU=435) was not explained only by Cr(VI) (24-h TU = 725 at $280\;mg\;L^{-1}$). Addition of nickel($29.5\;mg\;L^{-1}$) and copper ($26.5\;mg\;L^{-1}$) largely decreased the chromium toxicity up to 417 TU, indicating antagonistic interaction between heavy metals. This heavy metal interaction was successfully predicted by an equation of 24-h $TU\;=\;3.67\;{\times}\;\ln([Cu]\;+\;[Ni])\;+\;79.44$ at a fixed concentration of chromium.

• Environmental Analysis Health and Toxicology
• /
• 제28권
• /
• pp.2.1-2.7
• /
• 2013

Objectives Tricalcium phosphate and calcium hydrogenorthophosphate are high production volume chemicals, mainly used as foodstuff additives, pharmaceuticals, lubricants, synthetic resin, and disinfectants. Phosphate has the potential to cause increased algal growth leading to eutrophication in the aquatic environment. However, there is no adequate information available on risk assessment or acute and chronic toxicity. The aim of this research is to evaluate the toxic potential of phosphate compounds in the aquatic environment. Methods An aquatic toxicity test of phosphate was conducted, and its physico-chemical properties were obtained from a database recommended in the Organization for Economic Cooperation and Development (OECD) guidance manual. An ecotoxicity test using fish, Daphnia, and algae was conducted by the good laboratory practice facility according to the OECD TG guidelines for testing of chemicals, to secure reliable data. Results The results of the ecotoxicity tests of tricalcium phosphate and calcium hydrogenorthophosphate are as follows: In an acute toxicity test with Oryzias latipes, 96 hr 50% lethal concentration ($LC_{50}$) was >100 (measured:>2.14) mg/L and >100 (measured: >13.5) mg/L, respectively. In the Daphnia test, 48 hr 50% effective concentration ($EC_{50}$) was >100 (measured: >5.35) mg/L and >100 (measured: >2.9) mg/L, respectively. In a growth inhibition test with Pseudokirchneriella subcapitata, 72 hr $EC_{50}$ was >100 (measured: >1.56) mg/L and >100 (measured: >4.4) mg/L, respectively. Conclusions Based on the results of the ecotoxicity test of phosphate using fish, Daphnia, and algae, $L(E)C_{50}$ was above 100 mg/L (nominal), indicating no toxicity. In general, the total phosphorus concentration including phosphate in rivers and lakes reaches levels of several ppm, suggesting that phosphate has no toxic effects. However, excessive inflow of phosphate into aquatic ecosystems has the potential to cause eutrophication due to algal growth.

• Journal of Pharmaceutical Investigation
• /
• 제25권4호
• /
• pp.365-369
• /
• 1995

The acute cytotoxicities of chloroquine sulfate, propranolol, ascorbic acid, acetylsalicylic acid and acrylamide on cultured adult rat hepatocytes were evaluated by the use of LDH leakage and NR uptake test. On the basis of $IC_{50}$ values, the rank order of cytotoxicities of these drugs in both tests was chloroquine sulfate > propranolol > acetylsalicylic acid > ascorbic acid. The $IC_{50}$ of LDH test was very similar to that of NR uptake test. Thus, we concluded that both tests are reliable and sensitive methods in detecting toxicity in adult cultured rat hepatocytes.

• 한국산학기술학회논문지
• /
• 제17권11호
• /
• pp.701-707
• /
• 2016

열대지역과 같은 특정지역에서 오염물질의 독성평가 시, 그 지역의 생태환경에 적합한 위해성평가를 위해서는 그 지방 고유의 생물에 대한 독성실험이 요구된다. 따라서 본 연구는 열대에서 분리한 열대 요각류 Nitocra sp.를 독성실험생물로 사용하기 위해 이들을 안정적으로 배양/유지하기 위한 최적배양환경조건과 해양생태독성평가 가능성을 조사하였다. 최적 배양환경요인으로 수온, 염분 및 먹이에 대해 조사하였으며 생태독성평가는 급성독성과 만성독성 실험으로 나누어 실시하였다. 최적배양조건 실험데이터의 통계분석을 위해 One-way ANOVA test를 실시하였다. 최적배양환경조건을 조사한 결과, Nitocra sp.는 수온 $29^{\circ}C$, 염분 24~34‰에서 먹이로 Tetraselmis suecica를 공급하였을 때, 비교적 빠른 발달기간과 높은 생존율을 보였다. 최적배양조건을 바탕으로 구리와 비소에 대한 독성평가를 실시한 결과, 구리와 비소의 각 노출농도에 따라 민감하게 잘 반응해서 반수치사농도 즉 $LC_{50}$값과 영향을 미치지 않는 농도인 NOEC값을 얻을 수 있었다. 만성독성시험 결과, 구리와 비소노출 모두, 성비와 생산력은 유의적인 차이가 없었던 반면, 발달기간과 생존율은 농도에 따라 반응을 보였기 때문에 종말점으로 사용이 가능한 것으로 나타났다. 본 연구를 종합해 보았을 때, 열대 요각류인 Nitocra sp.는 열대 해양독성물질 평가를 위한 생태독성실험생물로 사용이 가능할 것으로 판단되며 차후 다양한 독성물질의 평가에 활용이 기대된다.