Download Risk profile Acetanilide and more Summaries Toxicology in PDF only on Docsity!
Risk profile Acetanilide Page 1 of 24
R I S K P R O F I L E
Ac eta nil ide
C A S N o. 1 0 3 - 8 4 - 4
D a t e o f r e p o r t i n g 2 6. 0 5. 2 0 1 1
Content of document
1. Identification of substance Page 1 2. Uses and origin Page 2 3. Regulation Page 5 4. Relevant toxicity studies Page 5 5. Exposure estimates and critical NOAEL/NOEL Page 7 6. Other sources of exposure than cosmetic products Page 8 7. Assessment Page 11 8. Conclusion Page 12 9. References Page 13 10. Annexes Page 15
1. Identification of substance
Chemical name (IUPAC): Acetanilide
INCI Acetanilid
Synonyms N-phenylacetamide
CAS No. 103 - 84 - 4
EINECS No. 203 - 150 - 7
Molecular formula C6H5NH(COCH3)
Chemical structure
Molecular weight (^) 135.
Contents (if relevant)
Physiochemical properties (^) Appearance: solid, white crystalline substance, Density: 1.22 g/cm^3 (20 °C) Boiling point: 304 °C (1013 hPa) Melting point: 115 °C Flash point: 173 °C DIN 51758 log Pow : 1,16 (no bioaccumulation; log Pow 1 - 3 ) Vapor pressure: 0.002 hPa (20 °C) Solubility (water): 5 g/l (20 °C) pH: 5 - 7 (at 10 g/l, H 2 O, 25 °C)
References: (1, 2)
Risk profile Acetanilide Page 2 of 24
2. Uses and origin
Uses Cosmetic products:
Functions according to
o CosIng database:
“Masking”- reduces or inhibits the basic odor or taste of the product
“Stabilizing” - improves ingredients or formulation stability and shelf-life
o In-market surveys by competent authorities
Perfuming (masking),
H 2 O 2 stabilizer in hair coloring /bleaching products and also in tooth whitening /bleaching products
Concentrations being applied
o Perfuming (masking) : maximally 0,025 % 1
o H 2 O 2 stabilizer / Tooth bleaching/whitening: 0.001 - 0.5 % 2. o H 2 O 2 stabilizer / Hair coloring: maximally 0.2 % in products placed on the scalp.
In Norway during the 80s, the cosmetics industry requested to use acetanilide as a stabilizer for H 2 O 2 in two-component hair coloring products, with one part containing H 2 O 2 and Acetanilide (up to 0.4 %) and the other part containing the dyestuff with auxiliary ingredients. These two components are normally mixed 1:1 before usage. According to the current Norwegian Cosmetics regulation (Norwegian Law and Jurisdiction), it is not allowed to use more than 0.2 % ( ppm) in the mixture being placed on the scalp. We cannot exclude that even in the market of today, consumers are exposed to products containing that much – or even more. The current regulation will be lifted 11 July 2013.
(^1) This figure is assumed taking into consideration that according to an earlier German cosmetic
products regulation no more than 0,025 % was allowed. If the concentration is higher the usage becomes unacceptable for health reasons applying an sufficiently high margin of safety of 100 (^2) Confer the USPTO Patent Application 20080044796, a teeth whitening system and a method for
whitening teeth. The application can be retrieved from the internet at the address: http://www.freshpatents.com/A-teeth-whitening-system-and-a-method-for-whitening-teeth- dt20080221ptan20080044796.php
Risk profile Acetanilide Page 4 of 24
concentration is above 0.1 %. No products or brands listed in the EWG cosmetic database (see EWG, 2011);
The limited listing of Acetanilide containing products we assume is due to the fact that most marketers think it not obligatory to declare auxiliary substances in raw material going into cosmetics as ingredients.
Food (data not retrieved)
Medicinal products /applications History: For many years after its discovery in 1886, Acetanilide was used as an alternative to aspirin (i.e. acetyl salicylate) - an analgesic (painkiller) and antipyretic (fever reducing) drug to relieve e.g. headache, menstrual pain, and rheumatic pain. Under the name “Acetanilide” it formerly appeared in the formula of a number of patent medicines and over the counter drugs. In 1948, Julius Axelrod and Bernard Brodie discovered that Acetanilide is much more toxic in these applications than other drugs, causing methemoglobinemia and ultimately causing damage to the liver and kidneys. Thus, Acetanilide has largely been replaced by less toxic drugs, in particular acetaminophen (i.e. paracetamol), which is a metabolite of Acetanilide and whose use Axelrod and Brodie suggested in the same study (8).
A product containing H 2 O 2 with Acetanilide (not over 0.017 per cent) is used in the treatment of rhus dermatitis (http://jama.ama- assn.org/content/146/7/612.extract)
Disinfectant: In the hospital sector Acetanilide appears to have been used with as much as 5000 ppm (i.e. 0.5 %) in H 2 O 2 solutions (19).
Other consumer products . Household products :
Acetanilide is one of the most frequently used stabilizers for hydrogen peroxide (H 2 O 2 ), at concentrations in the range of 25 - 250 ppm. http://www.foodgradeh2o2.com/101/247/typ/secure/ebv3.pdf
Origin Natural (exo /endo) Synthetic
Synthetic origin: Antipyretic analgesic drugs were derived as by-products of the German dye industry in the late nineteenth century, and Acetanilide was first made by Gerhardt in 1853 by reacting aniline with acetylchloride or acetic anhydride (2, 4, 5).
Risk profile Acetanilide Page 5 of 24
3. Regulation
Norway According to the current Norwegian Cosmetics it is not allowed to use more than 0.2 % (2000 ppm) in the mixture being placed on the scalp. The current regulation will be lifted 11 July 2013
EU Acetanilide is not mentioned in any of the annexes of the EU cosmetics directive.
It for a long time – but not anymore now - appeared in lists displaying drugs in some of the EU member states and so was allowed in cosmetics on specific terms only. In Germany, in earlier times the cosmetic industry was allowed to use acetanilide up till the low limit of 0.0025 % in fragrances. This national regulation no longer exists.
4. Relevant toxicity studies
Absorption Skin GI tractus
Theoretical default value equal to 100% is applied since no experimental values is available (section 5) (SCCS recommendation)
Distribution
Metabolism
Excretion
It was established in 1948 already that acetanilide is mainly metabolized to p-hydroksyacetanilide (paracetamol) in humans, and that paracetamol is responsible for the analgesic and antipyretic properties (7, 8).
Occurrence of methemoglobinemia and cyanosis after acetanilide administration is due to the small proportion of acetanilide being hydrolyzed to aniline in the human body (7).
Acetanilide is converted to a phenolic metabolite in the human body which gives it an analgesic effect, but some is converted to aniline (aminobenzene) which is toxic. It has been found that for a single dose of 10 mg/kg of acetanilide, the halflife in blood plasma is 191.5 ± 27.8 min. of in 25 subjects (human) and the metabolic clearance rate observed was 14.1 ± 2.8 liter/h of (Kellerman et al., 1978; cited in ref. 6).
Elimination of acetanilide takes place in two phases: first through oxidation to p-hydroxy acetanilide (paracetamol) in the liver, and then through the formation of water soluble glucuronide and sulphate conjugates (conjugation in the hydroxyl group), that is excreted in the urine (ca. 70-90 % of applied dose). Under normal circumstances, a limited amount of paracetamol is converted via the microsomal enzyme system to a toxic metabolite, NAPQI (N-acetyl-p-benzoquinone imine), which in turn is detoxicated by conjugation with reduced glutathione. If glutathione is depleted, covalent binding to macromolecules may lead to chronic hepatitis (hepatocellular necrosis), mainly related to abuse,
Risk profile Acetanilide Page 7 of 24
5. Exposure estimate and critical NOAEL / NOEL
NOAEL/NOEL critical Estimation of NOAEL is based on long term effects in animal experiments (OECD SIDS, ref. 6). Oral tube feeding of rats with acetanilide (12 /dose, males; 12/dose, females) at doses of 22, 67, 200 and 600 mg/kg/day over a period of 30 days (males) or 39- days (females).
Histopathological examinations demonstrated hyperplasia of blood cells in the spleen (”red pulp”; removal of damaged blood cells), hyperplasia of red blood cells in the bone marrow (most likely a compensatory response on hypoxia/anemia caused by acetanilide), as well as reduced values of hemoglobin and certain other blood parameters.
Interspecies variations are known to exist with regard to the effect of Acetanilide on the formation of hemoglobin, with reduced sensitivity in the order: cat > humans > dog > rat (10).
LOAEL for „repeated dose toxicity‟: 22 mg/kg/day (both sexes; rats) (6).
NOAEL (estimated) = LOAEL/3 (empirical factor of 3 is used when the exact value is missing) = 22 (mg/kg) /3 = 7 mg/kg
Exposure cosmetic products
Systemic exposure dose (SED) for Acetanilide in humans:
o Masking (“perfuming”) usage
Default values : cf. SCCS guide.
Skin area (total body) = 17800 cm^2 (SCCS) Amount of product applied pr. cm^2 : 1 mg (SCCS) Absorbance of product through the skin: 100 % (SCCS) Body weight: 60 kg (SCCNFP)
Maximum (earlier allowed) concentration of product for “masking”: 0.025 %
SED: 17800 mg (i.e.17800 cm^2 x 1 mg/cm^2 ) x 0.00025 / 60 kg = 0.074 mg/kg
o Tooth bleaching
Cf. Hydrogen peroxide, in its free form or when released, in oral hygiene products and tooth whitening products (SCCP/1129/07). For calculations - see Annex 4.
From the exposure studies, the systemic absorption of hydrogen peroxide is estimated to be in the range from 0.03 mg/kg bw/day to 0.2 mg /kg bw /day. Consequently, an exposure from tooth whitening products with 6% hydrogen peroxide of 0.2 mg /kg bw /day may be used in safety calculation.
For gel strips it has been reported that users occasionally may swallow the strip, resulting in an exposure of about 12 mg hydrogen peroxide (0.2 mg/kg bw).
Risk profile Acetanilide Page 8 of 24
The amount of gel: Y x 0,06 = 12 mg ; Y = 200 mg
Maximum concentration of Acetanilide being use in tooth bleaching products: 0,4 % (used for illustrative purpose)
SED (acetanilide): 200 x 0,004 = 0,8 mg or 0 .013 mg /kg bw /day
o Hair coloring products (oxidative hair dying)
50 g hair coloring product is applied to hair (default – SCCNFP)) 100 % skin absorbance (default; same as for fragrances /perfume)
Maximum concentration of Acetanilide in 1:1 mixture placed on the scalp: 0, 2 % (industry / application)
SED (acetanilide): 50000 x 0,002/60 = 1,7 mg /kg bw /day
Margin of Safety (MoS) MoS pertaining to current usage :
MoS for “masking” /perfuming: 7 /0.074 = 95
MoS for tooth bleaching: 7 / 0.013 = 538 ( The maximum allowed level corresponding to a MoS equal to 100 is 2.1 %.)
MoS for oxidative hair dying: 7/ 1,7 = 4, ( The maximum allowed level corresponding to a MoS equal to 100 is 0,0084 %.)
- Other sources of exposure than cosmetic products
Food stuffs No data retrieved
Pharmaceuticals Acetanilide is no longer used as a drug in its own right, but the success of its metabolite – paracetamol (acetaminophen) – is well known as a safer alternative (9). Thus, the following observations might be relevant for total exposure assessments.
Using painkillers such as ibuprofen, aspirin and paracetamol in pregnancy may harm development of the sex organs in unborn boys, warn Kristensen and coworkers (12). The condition known as cryptorchidism is a risk factor for reduced fertility and increased risk of testicular germ cell tumors later in life (12, 14-16). The second trimester is especially vulnerable, because the risk was doubled with ingestion of one analgesic drug during this period, and increased 16 times when more than one drugs were used simultaneously (16). Both the Danish and the Finnish cohort consisted of more than 2000 pregnant women. However, the lower limit for safe usage of these painkillers in relation to development of cryptochidism is not known.
Although the mechanism is not known, a separate study in rats appeared to confirm the link between painkillers and undescended testicles. It was also demonstrated that mild analgesics reduced levels
Risk profile Acetanilide Page 10 of 24
Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 52:28] o For pharmaceuticals of H 2 O 2 , an excellent stabilizer is 0.02 % quinine SO 4 o Acetanilide 0.03% is present in H 2 O 2 , to protect from it from the effects of sunlight, since it is light sensitive
http://bit.ly/hn0n
Adverse side effects apart from cosmetics
In 1948, Brodie & Axelrod (7) reported that Acetanilide users developed a non-lethal blood disease, known as methemoglobinemia, which was ascribed to the small proportion of Acetanilide that is hydrolyzed to aniline in the body. Methemoglobin is a modified molecular form of hemoglobin responsible for disrupting the normal ability of hemoglobin to transport oxygen, thereby causing functional anemia. Thus, while Acetanilide and paracetamol both are associated with increased risk for liver and kidney damage, Acetanilide is considered to be more toxic by also causing methemoglobinemia.
Examples of acute poisoning related to therapeutic usage or abuse of Acetanilide are known from the literature (7, 8), reviewed in a report by EC Joint Research Centre (JRC) (10). Symptoms: methemoglobinemia, cyanosise (blue coloring of the blood), hemolytic anemia and alterations in blood parameteres. Other key symptoms: increased temperature, increased heartrate, nausea, vomiting, followed by extreme cyanosis and slight jaundice over the whole body.
Reduced kidney function, liver failure and alcoholism results in increased risk for kidney- and liver damage related to usage of acetanilide (and paracetamol) (Biam2, ref. 8). Intake of ethanol inhibits microsomal oxidation and increases the half-life of acetanilide in the circulation (11).
Interaction : High doses of paracetamol increases INR*, resulting in increased risk for bleeding (http://www.legemiddelverket.no/templates/InterPage____82950.aspx)
*) INR: International normalized ratio; http://www.labtestsonline.org/understanding/analytes/pt/test.html
Risk profile Acetanilide Page 11 of 24
7. Assessment
The total exposure of acetanilide in the human body is the sum of contributions from cosmetic
products and other sources (e.g. environmental exposure and pharmaceutical drugs).
Presumably, Acetanilide is still used in a number of cosmetic products on the market today, perhaps
most frequently as a stabilizer of H 2 O 2 , most notably in hair coloring / bleaching products, but also in
cosmetic products for bleaching discolored nails and cleaning / peeling skin – although perhaps not
that much when it comes to the big brands. Probably, Acetanilide has to some extent been replaced
by less toxic H 2 O 2 stabilizers over the years (e.g. sodium stannate - Na 2 Sn(OH) 6 ). Data on the
extension to which Acetanilide has been replaced does not exist in the public domain.
Acetanilide as a H 2 O 2 stabilizer in tooth bleaching products is a potential new application area for this
substance; cf. Dahl J (NIOM, Norway).
In addition, acetanilide is also used as a “masking agent” (cf. CosIng database); i.e. it “perfumes” the
product by removing disagreeable smell from the product itself when added as an ingredient.
However, we have not been able to retrieve products in which acetanilide has this function.
The estimated NOAEL of 7 mg/kg/day for acetanilide with a MOS of approx. 100 is based on
cosmetics solely, and does not consider contributions from other sources.
Although acetanilide is no longer used as a pharmaceutical drug in its own right, the success of its
metabolite – paracetamol (a.k.a. acetaminophen) – is well known as a safer alternative (9). However,
paracetamol has the potential to cause serious side effects in humans, including increased risk for
liver necrosis (7, 8). Prolonged use of paracetamol in pregnancy has recently been reported to harm
development of the sex organs (i.e. cryptorchidism) in unborn boys (12, 16), thereby increasing the
risk for poor sperm quality and testicular cancer in later life.
A single paracetamol tablet (500 mg) contains more “endocrine disruptor potency” than the combined
exposure to the ten most prevalent of the currently known environmental endocrine disruptors during
the whole pregnancy, according to Dr. Leffers, a senior author of one of the Danish studies (12; see
also EC Cordis News, 2010, ref. 15). Nonetheless, the direct role of paracetamol in the etiology of
cryptorchidism remains to be established, and there is a gap in our knowledge concerning the lower
limit for safe usage of this and other mild analgesics in relation to this potential reprotoxic effect.
The environmental exposure to acetanilide is considered to be very low, and is most likely via direct
dermal contact and inhalation at the production site (only two geographic locations in Korea and the
US) (6). Likewise, we have not been able to retrieve data for acetanilide in food stuffs.
Risk profile Acetanilide Page 13 of 24
9. References
- Merck – MSDS according to Regulation (EC) nr. 1907/2006 (revised 10.11.2010). Cat.nr. 100011: Acetanilide test substance for elementary analysis. http://www.merck-chemicals.kr/pharmaceutical-ingredients/en_US/Merck-KR- Site/USD/ViewProductDocuments-File?ProductSKU=MDA_CHEM- 100011&DocumentType=MSD&DocumentId=%2Fmda%2Fchemicals%2Fmsds%2Fno- NO%2F100011_NO_NO.PDF&DocumentSource=GDS&Country=KR&Channel=Merck-KR-Site
- http://en.wikipedia.org/wiki/Acetanilide
- http://ec.europa.eu/consumers/cosmetics/cosing/index.cfm?fuseaction=search.details&id=
- http://www.yourdictionary.com/acetanilide
- Botting R (2004) Antipyretic therapy. Frontiers in Bioscience 9: 956-
- OECD SIDS (2003) Acetanilide, SIDS Initial Assessment Report, Geneva: United Nations Environment Programme, September 2003. http://webnet.oecd.org/hpv/ui/Default.aspx; www.inchem.org/documents/sids/sids/Acetanilide.pdf
- Brodie, B. B.; Axelrod, J. (1948), "The fate of acetanilide in man", J. Pharmacol. Exp. Ther. 94 (1): 29 – 38, PMID 18885611, http://profiles.nlm.nih.gov/HH/A/A/A/D/_/hhaaad.pdf
- http://www.biam2.org/accueil.html; http://www.biam2.org/www1/Sub1367.html http://translate.googleusercontent.com/translate_c?hl=no&sl=fr&u=http://www.biam2.org/www1/Sub 67.html&prev=/search%3Fq%3Dfrench%2Bbiam%2Bdatabase%26hl%3Dno%26prmd%3Divns&rurl=t ranslate.google.no&usg=ALkJrhj6Er_ZaWsLXbODcN9gPrFCmMjFrw#SubEII
- http://www.ask.com/wiki/Acetanilide
- http://ecb.jrc.ec.europa.eu/exportfiles/103-84-4.exp
- McKay J, Rawlings MD, Cobden I & James OFW (1982) The acute effects of ethanol on acetanilide disposition in normal subjects, and in patients with liver disease. Br. J. clin. Pharmac 14: 501-504.
11b. http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+ccris:@term+@rn+103-84-
- Kristensen, D. M., et al. (2010) Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Human Reproduction (in press), published online 8 Nov. DOI: 10.1093/humrep/deq323.
- http://www.forskning.no/artikler/2010/desember/274634/print
- http://www.forskning.no/artikler/2010/november/
http://cordis.europa.eu/fetch?CALLER=EN_NEWS_FP7&ACTION=D&DOC=2&CAT=NEWS&QUERY =012c39e73fea:6d92:4c017339&RCN=
- Jensen MS, Rebordosa C, Thulstrup AM, Toft G, Sørensen HT, Bonde JP, Henriksen TB, Olsen J. (2010) Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism. Epidemiology 21:779-85.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm239894.htm
Risk profile Acetanilide Page 14 of 24
- Vandenberghe J (1996). Hepatotoxicology: mechanisms of liver toxicity and methodological aspects. In: Niesink RJM, deVries J and Hollinger MA (eds.) Toxicology. Principles and Applications. CRC Press. pp. 707-708.
- ”American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,pp. 52:28”.
Risk profile Acetanilide Page 16 of 24
TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - man DOSE/DURATION : 59 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 85DCAI "Poisoning; Toxicology, Symptoms, Treatments," 2nd ed., Arena, J.M., Springfield, IL, C.C. Thomas, 1970 Volume(issue)/page/year: 2,73,
Dyr:
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 800 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 54,159,
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 540 mg/kg TOXIC EFFECTS : Nutritional and Gross Metabolic - body temperature decrease REFERENCE : JAPMA8 Journal of the American Pharmaceutical Association, Scientific Edition. (Washington, DC) V.29-49, 1940-60. For publisher information, see JPMSAE. Volume(issue)/page/year: 48,204,
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1210 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,20,
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE :
Risk profile Acetanilide Page 17 of 24
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: AD277-
TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : HBAMAK "Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig, Ger. Dem. Rep.) Volume(issue)/page/year: 4,1290,
TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 300 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : HBAMAK "Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig, Ger. Dem. Rep.) Volume(issue)/page/year: 4,1290,
TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - cat DOSE/DURATION : 250 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JPHAA3 Journal of the American Pharmaceutical Association. (Washington, DC) V.1-28, 1912-39; New series: V.1-17, 1961-77. Volume(issue)/page/year: 28,70,
TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - cat DOSE/DURATION : 8500 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JAPMA8 Journal of the American Pharmaceutical Association, Scientific Edition. (Washington, DC) V.29-49, 1940-60. For publisher information, see JPMSAE. Volume(issue)/page/year: 30,91,
TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 1500 mg/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - spastic paralysis with or without sensory
Risk profile Acetanilide Page 19 of 24
Annex 2. Systemic toxic effects
Excerpt summary table toxicological data (OECD SIDS, 2001): (ref 6) www.inchem.org/documents/sids/sids/Acetanilide.pdf
Risk profile Acetanilide Page 20 of 24
Annex 3: Paracetamol metabolism
