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Diss Factsheets

Ecotoxicological information

Endpoint summary

Administrative data

Description of key information

Short-term toxicity to fish

Based on the nominal concentrations, experimental median lethal concentration [LC-50 (96 h)] for Paracetamol (CAS No. -103-90-2) in Danio rerio was found to be  > 100 mg/L on the basis of mortality effects in a 96 hour study. Thus based on this LC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance Paracetamol does not exhibit toxicity to aquatic fish (Danio rerio).

 

Long-term toxicity to fish

Chronic toxicity of Paracetamol (acetaminophen) was evaluated using a fish (Oryzias latipes). The No-observable-effect-concentration (NOEC) value of acetaminophen in aquatic fish (Oryzias latipes) in a 90 days post fertilization study on various effects were reported as follows:

NOEC (90 dpf) = 95.0 mg/L (Survival)

LOEC (33 dpf) = 95.0 mg/L (Survival)

NOEC (19 dpf) = 95.0 mg/L (Survival)

NOEC (90 dpf) = 9.5 mg/L (Growth)

NOEC (90 dpf) = 9.5 mg/L (Relative organ weight)

NOEC (90 dpf) = 0.000095 to 9.5 mg/L (Vitellogenin)

NOEC (90 dpf) = 9.5 mg/L (Reproduction)

 

Short-term toxicity to aquatic invertebrates

The 48 h acute toxicity test with D. magna was conducted following OECD guideline 202 (1984). The 48 h D. magna EC50 value for paracetamol (acetaminophen) determined in the present study was 11.85 mg/L on the basis of mortality effect. Based on this EC50 value, the substance may qualify for the aquatic classification in the chronic 3 category. But paracetamol was found to be rapidly degradable and the BCF value was not >= 500. Also the partition coefficient the Log Kow was not >= 4. Thus considering the CLP Criteria for aquatic classification of the substance, it is concluded that Paracetamol shall not exhibit short term toxicity to aquatic invertebrate (Daphnia magna) i.e. it is non hazardous to the aquatic environment.

 

Long-term toxicity to aquatic invertebrates

Chronic toxicity of Paracetamol (acetaminophen) was evaluated using a crustacean (Daphnia magna) in a 21 day study. The No observable effect concentration (NOEC) value of acetaminophen in aquatic crustacean (Dapnia magna) in a 21 day study on various effects were reported as follows:

NOEC (21 days) = 5.72 mg/L (Survival)

NOEC (21 days) = 5.72 mg/L (Reproduction)

NOEC (21 days) = 5.72 mg/L (Population)

 

Toxicity to aquatic algae and cyanobacteria

The effect of test item paracetamol, CAS No. 103-90-2 was studied on the growth of fresh water green algaChlorella vulgaris.The study was conducted following OECD guideline 201- Alga, growth inhibition test. The test concentration chosen for the study were 6.25mg/l, 12.5mg/l, 25mg/l, 50mg/l, 100mg/l and 200mg/l. The test concentrations were prepared using stock solution of the test item using mineral media. The green alga was exposed to the test concentration for a period of 72 hours to observe average specific growth rate and % growth inhibition under the effect of the test item. EC50 calculated graphically through probit analysis was observed to be 112.666mg/l.Based on this EC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance Paracetamol does not exhibit toxicity to aquatic algae (Chlorella vulgaris).

 

Toxicity to microorganisms

The inhibition growth concentration (IGC50) value of Paracetamol in microorganism (Tetrahymena pyriformis) in a 46 hr study on the basis of growth inhibition effect was estimated  to be 189.00 mg/L.

Additional information

Short-term toxicity to fish

Based on the short term toxicity test conducted in compliance with the OECD guideline 203 by UERL(FT-/103-90-2/2016), the median lethal concentration [LC-50 (96 h)] was found to be > 100 mg/L. The study was carried out on zebra fish for 96 hrs. on the basis of mortality effects. 

In another study reported by Kim et.al (Environ. Int.33(3): 370-375),the LC50 was found to be >160mg/L after exposure to Oryzias latipes for 96 hrs.on the basis of mortality effect. 

Broderius et.al (Environ. Toxicol. Chem.14(9): 1591-1605) presented a 96hr short term study in Pimephales promelas indicating the LC50 to be 814mg/L. 

Similarly Brooke et.al (Superior, WI: Center for Lake Superior Environmental Studies Univ. of Wisconsin Superior, 1984. p.291) along with the other reliable database sources indicated the LC50 to be 814 mg/L. 

As determined by the prediction model Danish QSAR and Etox database the LC50 values were found to be found to be 334.15 mg/l and >1000mg/l respectively. 

A fish early-life stage test was used to assess the toxicity of paracetamol by K.-P. Henschel(1997). Based on mortality induced in embryos of the zebrafish after exposure, the EC50 was estimated to be 378 mg/L based on Probit analysis of the dose-response curve.

 

Thus from the above studies available for the the target substance Paracetamol, the LC50 values was found to be ranging between >100 mg/L to >1000 mg/L in a 96 hrs. study on the basis of mortality effect. Thus, it is concluded that Paracetamol does not exhibit short term toxicity to aquatic fish i.e. it is non-hazardous to the aquatic environment for the purpose of classification of the substance as per the new CLP guidelines.

 

Long-term toxicity to fish

Chronic toxicity of acetaminophen was evaluated using a fish (Oryzias latipes). The nominal concentrations selected for the study were 0, 0.000095, 0.00095, 0.0095, 0.095, 0.95, 9.5 and 95.0 mg/L. The effects on survival, growth, relative organ weight, vitellogenesis and the reproduction capacity of the fish were observed in a study. In the chronic fish toxicity test, significant reduction in juvenile survival was observed at 30 d post-hatch (dph) at 95 mg/L of acetaminophen. After the exposure to acetaminophen, vitellogenin levels tended to increase in male fish at 90 dph. In the eggs which were prenatally exposed to 9.5 mg/L of acetaminophen, reduced hatchability was observed.

 

Thus , the No-observable-effect-concentration (NOEC) value of acetaminophen in aquatic fish (Oryzias latipes) in a 90 days post fertilization study on various effects were reported as follows:

NOEC (90 dpf) = 95.0 mg/L (Survival)

LOEC (33 dpf) = 95.0 mg/L (Survival)

NOEC (19 dpf) = 95.0 mg/L (Survival)

NOEC (90 dpf) = 9.5 mg/L (Growth)

NOEC (90 dpf) = 9.5 mg/L (Relative organ weight)

NOEC (90 dpf) = 0.000095 to 9.5 mg/L (Vitellogenin)

NOEC (90 dpf) = 9.5 mg/L (Reproduction)

 

Our observations suggest however that ecological risks of Paracetamol (acetaminophen) is negligible at the concentrations currently found in the environment.

 

Short-term toxicity to aquatic invertebrates

 

Kim,P. et.al (2012) studied the 48 h acute toxicity test with D. magna and Moina macrocopa following OECD guideline 202 (1984).EC50 value determined in the present study was 11.85 mg/L and 56.34 mg/L on the basis of mortality effect. 

Based on the short term toxicity test conducted by Ministry of the Environment in Japan/J-CHECK database.The tests are conducted based on OECD-GLP standard and OECD test guidelines.The median effective concentration (EC50) in Daphnia magna was found to be 3.5 mg/L in a 48 hour study. 

In another study conducted by Guk h. Han et.al (2006),the lethal concentration (LC50) reported as 20.1 mg/L on the basis of mortality effects in a 48 hour study.

In the study reported by K.-P. Henschel et.al ((1997)), A Daphnia magna chemical toxicity test was performed: “according to OECD Guideline 202”. The resulting dose-response curve was used to evaluate the level of toxicity to D. magna after 48 hours. The effect concentration (EC50) after 48 hours was reported as 50 mg/L.

Similarly Henrik Lilius et.al (1995) conducted the study on daphnia pulex for 24 hrs indicate the effective concentration (EC50) value of Paracetamol as 136 mg/L; based on intoxication effect .

In the study of Calleja, M. C. et.al (1994) ,the lethal concentration (LC50) in aquatic invertebrate (Daphnia magna) in a 24 hr study on the basis of immobility effects was found to be 269.153 mg/L.

 As determined by the Etox database, the lethal concentration (LC50) in aquatic invertebrate (Artemia salina) in a 24 hr study on the basis of mobility effect was found to be 578 mg/L.

 

Based on the above studies available for the substance Paracetamol (acetaminophen), the EC50 is ranging from 3.5 to 136 mg/L and LC50 is ranging from 20.1 to 578 mg/L in aquatic invertebrates in a 24 to 48 hours study on the basis of various effects such as mortality, intoxication, immobility etc. Based on some of this EC50 and LC50 value, the substance may qualify for the aquatic classification in the chronic 2 category and chronic 3 category. But Paracetamol was found to be rapidly degradable and the BCF value was not >= 500. Also the partition coefficient the Log Kow was not >= 4. Thus, it is concluded that Paracetamol shall not exhibit short term toxicity to aquatic invertebrate i.e. it is non-hazardous to the aquatic environment for the purpose of classification of the substance as per the new CLP guidelines.

 

Long-term toxicity to aquatic invertebrates

Kim,P. et.al (Chemosphere89(1): 10-18) studied Chronic toxicity of Paracetamol (acetaminophen) using freshwater organisms including crustaceans (Daphnia magna and Moina macrocopa). The effects of long-term exposure on D. magna ad M. macrocopa were assessed following OECD guideline 211. In 21 d D. magna exposure, the No observable effect concentration (NOEC) on various effects were reported as NOEC = 5.72 mg/L (Survival, Reproduction and Population). Whereas in 7 d M. macrocopa exposure, the lowest observed effect concentration (LOEC) on various effects were reported as LOEC = 25.75 mg/L (Survival) and 0.95 mg/L (Reproduction).

 

Based on the long term toxicity test conducted by Ministry of the Environment in Japan/J-CHECK database. The tests are conducted based on OECD-GLP standard and OECD test guidelines. The median effective concentration (EC50) and the No-observable-effect-concentration (NOEC) value of Paracetamol in aquatic invertebrate (Daphnia magna) in a 21days study on the basis of reproduction effect was reported as 3.5 mg/L and 0.46mg/L according to a D. magna reproduction test.

 

In another study reported by Laira L. et.al ( Drug and chemical toxicoloy 2015 Informa Healthcare USA, Inc. DOI: 10.3109/01480545.2015.1029048), the No-observable-effect-concentration (NOEC) reported as 1.25 mg/L in Daphnia magna in a 21days study on the basis of immobilisation effect.

 

Our observations suggest however that ecological risks of Paracetamol (acetaminophen) is negligible at the concentrations currently found in the environment.

 

Toxicity to aquatic algae and cyanobacteria

The effect of test substance Paracetamol, CAS No. 103-90-2 was studied on the growth of fresh water

green alga Chlorella vulgaris. The study was conducted following OECD guideline 201- Alga growth inhibition test.The green alga (Chlorella vulgaris) was exposed to the test concentration for a period of 72 hours to observe average specific growth rate and % growth inhibition under the effect of the test item. EC50 calculated graphically through probit analysis was observed to be 112.666 mg/L. 

Based on the study conducted using the prediction model of QSAR, the median effective concentration (EC50) was estimated to be 169 mg/L. 

In another study conducted by Wiegel et.al (Arzneistoffe in Elbe und Saale; VII, 123 und Anhang; 2003),the 72hr EC50 to be 134mg/l in Pseudokirchnerella subcapitata on the basis of growth rate effect. 

Also the data from the report of Ministry of the Environment, Japan and J-CHECK database, indicates the median effective concentration (EC50) and the

No-observable-effect-concentration (NOEC) in a 72 hours study on the basis of growth rate and AUG effect was reported as 150 to >460 mg/L and 22.0 to 46.0 mg/L .

Based on the above studies available for the substance Paracetamol ,the EC50 is ranging from 112.666 to >460 mg/L and NOEC is ranging from 22.0 to 46.0 mg/L in aquatic algae in a 72 hour study on the basis of various effects such as growth rate effect and AUG effect. Thus, it is concluded that Paracetamol does not exhibit toxicity to aquatic algae i.e.it is non-hazardous to the aquatic environment for the purpose of classification of the substance as per the new CLP guidelines.

 

Toxicity to microorganisms

Based on the study conducted using the prediction model of DEPA, the inhibition growth concentration (IGC50) in microorganism (Tetrahymena pyriformis) in a 46 hr study on the basis of growth inhibition effect was estimated to be 189.00 mg/L.

Also data from Koch, H. P. et al (1993),the inhibition concentration (IC50) in Saccharomyces cerevisiae was found to be 92 mg/L.

In another study conducted by Rhone Poulenc Chimie Courbevoie Cedex,the effective concentration (EC0) in microorganism (anaerobic bacteria from a domestic water treatment plant) in a 24 hr study by Fermentation tube method was found to be 2000 mg/L.

Thus from the above studies available for the the target substance Paracetamol, the IGC50 and IC50 values for microorganism is ranging from 92 - 189 mg/L for various effects also EC0 was reported as 2000 mg/L.