Benzotrichloride: Difference between revisions

{{Chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 443418799

| ImageFileL1 = Benzotrichloride.png

| ImageSizeL1 = 105

| ImageAltL1 = Skeletal formula of benzotrichloride

| ImageFileR1 = Benzotrichloride-3D-balls.png

| ImageSizeR1 = 135

| ImageAltR1 = Ball-and-stick model of the benzotrichloride molecule

| PIN = (Trichloromethyl)benzene

| OtherNames = Toluene trichloride<br>Phenyl chloroform<br>α,α,α-Trichlorotoluene<br>PhCCl3

|Section1={{Chembox Identifiers

| CASNo_Ref = {{cascite|correct|CAS}}

| PubChem = 7367

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| UNII_Ref = {{fdacite|correct|FDA}}

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| ChEMBL = 1347516

| ChEBI = 82274

| EC_number = 202-634-5

| UNNumber = 2226

}}

|Section2={{Chembox Properties

| Odor = unpleasant

| MeltingPtC = -5.0

| MeltingPt_notes =

| BoilingPtC = 220.8

| BoilingPt_notes =

| pKb =

}}

|Section7={{Chembox Hazards

| MainHazards = potential occupational carcinogen

| NFPA-S =

| GHSPictograms = {{GHS05}}{{GHS06}}{{GHS07}}{{GHS08}}

| GHSSignalWord = Danger

| HPhrases = {{H-phrases|302|305|315|318|331|335|350}}

| PPhrases = {{P-phrases|201|202|261|264|270|271|280|281|301+312|302+352|304+340|305+351+338|308+313|310|311|312|321|330|332+313|362|403+233|405|501}}

| LD50 = 120 mg/kg (in rats){{CN|date=February 2023}}

| FlashPtC = 97.22

| AutoignitionPtC = 420

| PEL =

}}

'''Benzotrichloride''' ('''BTC'''), also known as '''α,α,α-trichlorotoluene''', '''phenyl chloroform''' or '''(trichloromethyl)benzene''', is an organic compound with the formula C₆H₅CCl₃. Benzotrichloride is an unstable, colorless or somewhat yellowish, viscous, [[organochlorine chemistry|chlorinated hydrocarbon]] with a penetrating odor. Benzotrichloride is used extensively as a chemical [[Reaction intermediate|intermediate]] for products of various classes, i.e. dyes and [[Antimicrobial|antimicrobial agents]].<ref name="Yasuo 143–150">{{Cite journal|last1=Yasuo|first1=Kimie|last2=Fujimoto|first2=Sachiko|last3=Katoh|first3=Masanobu|last4=Kikuchi|first4=Yoshiaki|last5=Kada|first5=Tsuneo|date=1978-11-01|title=Mutagenicity of benzotrichloride and related compounds|journal=Mutation Research/Genetic Toxicology|language=en|volume=58|issue=2|pages=143–150|doi=10.1016/0165-1218(78)90003-4|pmid=106269|issn=0165-1218}}</ref>

== Structure and reactivity ==

Benzotrichloride is a poorly water-soluble, clear to yellowish liquid with a penetrating odor. It hydrolyzes rapidly to [[benzoic acid]] and hydrochloric acid with a [[Half-life|half life]] of about 2.4 minutes, thus making the compound unstable in the presence of water.<ref name=":0">{{Cite journal|date=2004-01-23|title=α,α,α-Trichlorotoluene (Trichloromethylbenzene)|url=https://hpvchemicals.oecd.org/ui/handler.axd?id=62E27C06-0D36-49E5-AE11-2D65EA41D3F9|journal=OECD Sids}}</ref> In other chemical reactions, benzotrichloride reacts at the chlorinated [[Alpha and beta carbon|α-carbon]], for example in substitution reactions. It is used as an intermediate in the synthesis of [[benzoyl chloride]], [[Trifluorotoluene|benzotrifluoride]] and [[2,4-dihydroxybenzophenone]] which in turn are also intermediates in other reactions:<ref name=":0" />

:C₆H₅CCl₃ + resorcinol → 2,4-dihydroxybenzophenone<ref>{{Cite journal|last=Ponder|first=Fernando J|date=12 January 1968|title=Synthesis of 2-hydroxy-4-alkoxybenzophenones|url=https://patentimages.storage.googleapis.com/93/97/e0/65b454ae4092b2/US3526666.pdf|journal=United States Patent Office}}</ref><ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/8572|title=2,4-Dihydroxybenzophenone|last=PubChem|website=pubchem.ncbi.nlm.nih.gov|language=en|access-date=2020-03-20}}</ref>

: C₆H₅CCl₃ + H₂O → C₆H₅C(O)Cl + 2 HCl<ref name="Ullmann">{{cite journal|last1=Rossberg|first1=Manfred|last2=Lendle|first2=Wilhelm|last3=Pfleiderer|first3=Gerhard|last4=Tögel|first4=Adolf|last5=Dreher|first5=Eberhard-Ludwig|last6=Langer|first6=Ernst|last7=Rassaerts|first7=Heinz|last8=Kleinschmidt|first8=Peter|last9=Strack|first9=Heinz|last10=Cook|first10=Richard|last11=Beck|first11=Uwe|date=2006|title=Chlorinated Hydrocarbons|journal=Ullmann's Encyclopedia of Industrial Chemistry|page=139|doi=10.1002/14356007.a06_233.pub2|isbn=3527306730|last15=Beutel|first14=Eckhard|last16=Mann|first16=Trevor|last14=Löser|first13=Theodore R.|last13=Torkelson|first12=Karl-August|last12=Lipper|first15=Klaus K.}}</ref>

: C₆H₅CCl₃ + 3 KF → C₆H₅CF₃ + 3 KCl<ref>{{cite journal|last1=Bonath|first1=B.|last2=Förtsch|first2=B.|last3=Saemann|first3=R.|date=1966|title=Kinetische Untersuchung einer Seitenkettenchlorierung unter Verwendung eines Analogcomputers|journal=Chemie Ingenieur Technik|volume=38|issue=7|pages=739–742|doi=10.1002/cite.330380711}}</ref>

These compounds are further used to synthesize chemicals needed in the pharmaceutical industry ([[benzoyl peroxide]]), the synthesis of pesticides, dyes and UV-absorbing compounds which are often used in paint and plastics to prevent [[UV degradation|degradation by sunlight]].<ref name=":0" />

==Production==

Production capacity of benzotrichloride was estimated at 80,000 tonnes for the year 2000. It is produced by the [[free radical halogenation|free radical chlorination]] of [[toluene]], catalysed by light or [[radical initiator]]s such as [[dibenzoyl peroxide]]. Mono- and di-chlorinated intermediates are observed as [[benzyl chloride]] and [[benzal chloride]]:<ref name=":0" />

: C₆H₅CH₃ + Cl₂ → [[Benzyl chloride|C₆H₅CH₂Cl]] + HCl

: C₆H₅CH₂Cl + Cl₂ → [[Benzal chloride|C₆H₅CHCl₂]] + HCl

: C₆H₅CHCl₂ + Cl₂ → C₆H₅CCl₃ + HCl

== Regulation ==

Benzotrichloride is classified as an [[EPA list of extremely hazardous substances|extremely hazardous substance]] in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and hence its use is subject to a list of reporting requirements by companies or institutions which synthesize, store or use it in large quantities. In 2018, EU member states have approved a European Commission proposal to restrict the use of carcinogenic, [[mutagen]]ic and [[Reproductive toxicity|reprotoxic]] (CMR) substances in clothing, textiles and footwear. In 2015, the Commission published a preliminary list of 286 CMRs it proposed to restrict. Benzotrichloride was listed in this document as a toxic and carcinogenic compound.<ref>{{Cite web|url=https://chemicalwatch.com/66376/eu-member-states-back-cmr-restrictions-in-clothing-textiles|title=EU member states back CMR restrictions in clothing, textiles|website=Chemical Watch|language=en|access-date=2020-03-20}}</ref>

According to the harmonised classification and labelling (CLP00) approved by the European Union (EU), this substance is toxic if inhaled, causes serious eye damage, may cause cancer, causes skin irritation, is harmful if swallowed, and may cause respiratory irritation.<ref>{{Cite web|url=https://echa.europa.eu/substance-information/-/substanceinfo/100.002.395|title=α,α,α-trichlorotoluene - Substance Information - ECHA|website=echa.europa.eu|language=en-GB|access-date=2020-03-20}}</ref>

== Metabolism ==

In a rat experiment with [[Radioactive tracer|radiolabeled]] [14C]-benzotrichloride a single 40&nbsp;mg/kg body weight dose was administered. The absorption half-life of BTC from the gastrointestinal tract was determined to be 3 hours. The concentration in the blood peaked at 4 h reaching 6.5 ppm, this decreased to 2.6 ppm after 24 h. The elimination of half-life in blood was 22 h. Elimination took place for 90% through urine and 10% through faeces. After 72 hours 1.5% of the dose was still present in tissue. The highest concentration levels were present in liver, kidney and fat.<ref name=":0" />

BTC is rapidly metabolised via hydrolysis to [[benzoic acid]] and [[hydrochloric acid]]. This benzoic acid is first metabolized into benzoyl-CoA, which is metabolized into [[hippuric acid]] by replacing CoA with [[glycine]]. This [[hippuric acid]] is then excreted.<ref>{{Cite journal|last1=Irwin|first1=Cindy|last2=Reenen|first2=Mari van|last3=Mason|first3=Shayne|last4=Mienie|first4=Lodewyk J.|last5=Westerhuis|first5=Johan A.|last6=Reinecke|first6=Carolus J.|date=2016-12-01|title=Contribution towards a Metabolite Profile of the Detoxification of Benzoic Acid through Glycine Conjugation: An Intervention Study|journal=PLOS ONE|language=en|volume=11|issue=12|pages=e0167309|doi=10.1371/journal.pone.0167309|issn=1932-6203|pmc=5132330|pmid=27907139|bibcode=2016PLoSO..1167309I|doi-access=free}}</ref> 90% of the BTC was recovered from  the rat urine as [[hippuric acid]] while small amounts of benzoic acid (0.7%) and [[Phenylacetic acid|phenyl acetic acid]] (0.8%) were also present. Four unidentified metabolites (5.5%) were also present in urine.<ref name=":0" />

== Toxicity ==

=== Signs of toxicity ===

Several symptoms are related to the tested exposure to benzotrichloride (BTC) in rats: irritation of the eyes, the skin and the respiratory tract. Under occlusive conditions, rabbit skin which was exposed to BTC showed irritation. Next, severe eye irritation was reported in rabbits, after administering 0.1 mL of BTC. This eye irritation lasted up to 7 days. Finally, several rat studies into the [[Acute toxicity|acute toxic effects]] indicate that the respiratory system will be irritated after inhalation or oral uptake of BTC.<ref name=":0" />

The effects of repeated inhalation, estimated with experiments on rats, include the following. BTC can lead to [[bronchitis]] and [[bronchopneumonia]], depressed weight gain and gasping. Microscopically, [[inflammation]] and [[squamous metaplasia]] of the cells lining the nasal, tracheal, bronchial and bronchiolar epithelium can occur in rats. Histopathologically, an increased incidence of portal inflammatory cells infiltrate the [[liver]] and also [[bile]] duct proliferation is likely to occur.<ref>{{Cite journal|last1=Warheit|first1=D. B.|last2=Carakostas|first2=M. C.|last3=Kelly|first3=D. P.|last4=Hartsky|first4=M. A.|date=April 1991|title=Four-week inhalation toxicity study with Ludox colloidal silica in rats: pulmonary cellular responses|journal=Fundamental and Applied Toxicology|volume=16|issue=3|pages=590–601|doi=10.1016/0272-0590(91)90098-o|issn=0272-0590|pmid=1649779}}</ref>

The toxicity of BTC in mammals was assessed by Chu I. et al. (1984) by tracking several characteristics in rats for 28 days after oral intake of BTC. Growth rate and food consumption were not found to be affected by treatment. No deaths occurred during these trials.<ref name="Chu 183–191">{{Cite journal|last1=Chu|first1=I.|last2=Shen|first2=S. Y.|last3=Villeneuve|first3=D. C.|last4=Secours|first4=V. E.|last5=Valli|first5=V. E.|date=March 1984|title=Toxicity of trichlorotoluene isomers: a 28-day feeding study in the rat|journal=Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes|volume=19|issue=2|pages=183–191|doi=10.1080/03601238409372424|issn=0360-1234|pmid=6736562}}</ref>

=== Animal toxicity ===

==== Acute toxicity ====

===== Inhalation =====

Inhaling 1147&nbsp;mg/m³ of benzotrichloride (BTC) for 3 hours resulted in 1 out of 6 male rats dying (after 3 days). On the other hand, inhaling 995&nbsp;mg/m³ of BTC for 3 hours resulted in 4 out of 6 female rats dying within 13 days. However, reducing the duration of exposure to only one hour with a concentration just above 800&nbsp;mg/m³ resulted in no male or female rats dying. The treated rats had irritated oral and ocular mucous membranes, while behaviour and breathing were altered for up to 13 days.<ref name=":0" />

===== Dermal =====

Out of 10 female rats 1 died after being exposed to 5000&nbsp;mg/kg body weight of BTC. This indicates that the [[Median lethal dose|median lethal dosage]], the LD₅₀ value, is higher than 5000&nbsp;mg/kg body weight. The rats showed sedation starting from day 1 until day 8-10.<ref name=":0" />

===== Oral =====

Studying 15 male and 15 female rats per dose group, after being given an oral dosage, an LD₅₀ of 2188&nbsp;mg/kg bodyweight and an LD₅₀ of 1590&nbsp;mg/kg bodyweight were found for males and females, respectively. Laboured breathing, [[polyuria]], sanguineous urine, and reduced activity were observed, lasting from 15 minutes after ingestion until 7–9 days. The deceased rats had empty intestinal tracts and white-stippled stomachs.<ref>{{Cite web|url=https://echa.europa.eu/nl/registration-dossier/-/registered-dossier/2060/7/3/2|title=α,α,α-trichlorotoluene - Registration Dossier - ECHA|website=echa.europa.eu|language=nl-NL|access-date=2020-03-20}}</ref><ref name=":0" /> Moreover, pure compound administration resulted in a male LD₅₀ of 1249&nbsp;mg/kg body weight. Symptoms in these male rats included: bloody eyes, [[ataxia]], cramps, [[diuresis]], weight loss.<ref name=":0" /> Another study found an LD₅₀ of 770&nbsp;mg/kg (male) and 702&nbsp;mg/kg (female) after administering these rats with benzoyl chloride in corn oil. Besides the same symptoms described earlier, upon [[Autopsy#Other animals .28necropsy.29|necropsy]] lung congestion, [[thymus]] with red foci and yellow stained [[Genitourinary system|urogenital]] region and fluid filled intestines were found.<ref name=":1">{{Cite journal|last1=Takahashi|first1=N.|last2=Kadota|first2=T.|last3=Kawano|first3=S.|last4=Ishikawa|first4=K.|last5=Kuroyanagi|first5=K.|last6=Hamajima|first6=Y.|last7=Ohta|first7=K.|last8=Ohta|first8=S.|last9=Kai|first9=S.|last10=Kohmura|first10=H.|date=April 1986|title=[Toxicity studies of VP 16-213 (I)--Acute toxicity in mice, rats and rabbits]|journal=The Journal of Toxicological Sciences|volume=11 Suppl 1|pages=1–16|doi=10.2131/jts.11.supplementi_1|issn=0388-1350|pmid=3761389|doi-access=free}}</ref>

=== Repeated dose toxicity ===

==== Inhalation ====

The toxic effects of repeated benzotrichloride exposure have been assessed for inhalation, dermal exposure and oral ingestion. After repeated exposure to a concentration of 12.8&nbsp;mg/m³ twice weekly for 30 minutes, over 12 months in mice, severe [[bronchitis]] and bronchial [[pneumonia]] were observed.<ref name="Yoshimura 352–359">{{Cite journal|last1=Yoshimura|first1=H.|last2=Takemoto|first2=K.|last3=Fukuda|first3=K.|last4=Matsushita|first4=H.|date=September 1986|title=[Carcinogenicity in mice by inhalation of benzotrichloride and benzoyl chloride]|journal=Sangyo Igaku. Japanese Journal of Industrial Health|volume=28|issue=5|pages=352–359|doi=10.1539/joh1959.28.352|issn=0047-1879|pmid=3820773|doi-access=free}}</ref> After exposure of 5.1&nbsp;mg/m³ for 6 hours a day, 5 days a week for 4 weeks, no adverse effects were observed in rats.<ref name=":1" /> Note that the exposure times resemble a 5-day work week (although with only 30 hours).

==== Dermal ====

After dermal administration in rabbits between 50 and 200&nbsp;mg/kg bodyweight per day (5 days a week, 3 weeks) skin irritation up to [[necrosis]] was observed, suggesting that it is a dermal irritant.<ref name=":0" />

==== Oral ====

After feeding rats 0.048–53&nbsp;mg/kg body weight for 28 days, only mild microscopical liver kidney and thyroid structure change was observed, even at the lowest dose.<ref name="Chu 183–191"/> The data presented in this study suggest that BTC possess a low order of oral toxicity in the rat.<ref name="Chu 183–191"/>

=== Mutagenicity and carcinogenicity ===

==== Inhalation ====

[[Genotoxicity|Genotoxic]] potential was shown in bacteria and mammalian cell system, [[micronucleus]] formation occurred in bone marrow cells. Actual cancer incidence increase was clearly observed too: The same study finding [[bronchitis]] after long term respiratory use, found that 81% of mice had lung [[adenoma]]s(8% in control), 27% skin adenomas (0% in control), 11% malignant [[lymphoma]]s (0% in control).<ref name="Yoshimura 352–359"/> Similar studies also showed significant carcinogenicity.<ref name=":0" /> This shows that even though long-term inhalation damages the lungs, it also increases cancer risk, which is a risk needing stricter regulation.

==== Dermal ====

Dermal and oral studies all showed significant lung cancer increase, together with either significant skin cancer and stomach cancer increase respectively.<ref>{{Cite journal|last1=Fukuda|first1=K.|last2=Matsushita|first2=H.|last3=Sakabe|first3=H.|last4=Takemoto|first4=K.|date=October 1981|title=Carcinogenicity of benzyl chloride, benzal chloride, benzotrichloride and benzoyl chloride in mice by skin application|journal=Gan|volume=72|issue=5|pages=655–664|issn=0016-450X|pmid=7327367}}</ref> Research, after suspicion of carcinogenicity in benzoyl-chloride producing factories, on [[Laboratory mouse|ICR mice]] also showed significant incidence of tumors: skin-cancer(68%) and pulmonary tumors(58%) after applying 2.3 microliter/animal twice weekly for 50 weeks.<ref>{{Cite web|url=https://www.sigmaaldrich.com/catalog/papers/7327367|title=Carcinogenicity of benzyl chloride, benzal chloride, benzotrichloride and benzoyl chloride in mice by skin application. {{!}} Sigma-Aldrich|website=www.sigmaaldrich.com|access-date=2020-03-20}}</ref>

==== Oral ====

In humans only a few cases of lung cancer are linked to either [[benzoyl chloride]] or benzotrichloride, although smoking also might have played a role.<ref>{{Cite journal|last1=Sakabe|first1=Hiroyuki|last2=Matsushita|first2=Hidetsuru|last3=Koshi|first3=Shigezi|date=1976|title=Cancer Among Benzoyl Chloride Manufacturing Workers|journal=Annals of the New York Academy of Sciences|language=en|volume=271|issue=1|pages=67–70|doi=10.1111/j.1749-6632.1976.tb23094.x|pmid=1069541|bibcode=1976NYASA.271...67S|s2cid=26430038|issn=1749-6632}}</ref> Both NCI thesaurus and NPT carcinogen reports classify BTC as “reasonably anticipated to be a human carcinogen”, based on limited evidence of carcinogenicity from studies in humans and sufficient evidence of carcinogenicity from studies in experimental animals.<ref>{{Cite web|url=https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C29811|title=NCI Thesaurus|website=ncit.nci.nih.gov|access-date=2020-03-20}}</ref><ref>{{Cite web|url=https://ntp.niehs.nih.gov/ntp/roc/content/profiles/benzotrichloride.pdf|title=Acrobat Accessibility Report|last=Administrator|website=ntp.niehs.nih.gov|language=en-us|access-date=2020-03-20}}</ref>

==== Aquatic effects ====

[[Daphnia magna]] (a planktonic crustacean) were tested, 24 h-[[EC50]] of 50&nbsp;mg/L was found. The toxic effects were attributed to [[Hydrogen chloride|HCl]] formation, as benzotrichloride dissociates rapidly into the far less toxic [[benzoic acid]] and HCl on water exposure. Compensating the pH decrease in water from the HCl negated toxic effects, suggesting that water acidification is the reason for the low aquatic life toxicity.<ref>{{Cite book|last=Bringmann G and Kuehn R|title=Befunde der Schadwirkung wassergefaehrdender Stoffe gegen Daphnia magna|publisher=Z. Wasser- Abwasser-Forsch.|year=1977|pages=10 (5), 161–166}}</ref> Benzoic acid has an EC50 of >100&nbsp;mg/L towards aquatic life, is readily biodegradable and does not accumulate, so is not regarded as toxic towards aquatic life.

=== Fertility ===

No extensive studies were done on fertility effects. As the carcinogenic potential on its own already warrants extensive restrictions, no additional restrictions are needed for effect on fertility, although the genotoxic properties suggest that fertility might be affected.<ref name=":0" />

== Mechanism of toxicity ==

Part of the toxicity of benzotrichloride can be explained by its [[hydrolysis]] to [[benzoic acid]], whose further metabolism can cause toxic effects. [[Benzoyl-CoA]] formation can deplete [[acetyl-CoA]] levels, hampering processes requiring acetyl-CoA, like [[gluconeogenesis]] via [[pyruvate carboxylase]].<ref name=":2">{{Cite journal|last1=Tremblay|first1=George C.|last2=Qureshi|first2=Ijaz A.|date=1993-01-01|title=The biochemistry and toxicology of benzoic acid metabolism and its relationship to the elimination of waste nitrogen|journal=Pharmacology & Therapeutics|language=en|volume=60|issue=1|pages=63–90|doi=10.1016/0163-7258(93)90022-6|pmid=8127924|issn=0163-7258}}</ref> Hepatic [[Adenosine triphosphate|ATP]] levels are also lowered by 70-80%, at doses of 720–1440&nbsp;mg/kg benzoic acid via [[intraperitoneal injection]], by reducing acetyl-CoA availability for ATP production, which can have a wide range of consequences for affected cells.<ref name=":2" /> Ammonia toxicity can be amplified by benzoic acid, as it inhibits ureagenesis, reducing ammonia detoxification. Furthermore, benzoic acid can displace [[bilirubin]] from the [[albumin]]s, posing a risk of bilirubin toxicity, as it diffuses into tissues.<ref name=":2" />

[[Benzoic acid]] was shown to be genotoxic in vitro.<ref>{{Cite journal|last1=Yılmaz|first1=Serkan|last2=Ünal|first2=Fatma|last3=Yüzbaşıoğlu|first3=Deniz|date=2009-07-30|title=The in vitro genotoxicity of benzoic acid in human peripheral blood lymphocytes|journal=Cytotechnology|language=en|volume=60|issue=1|pages=55|doi=10.1007/s10616-009-9214-z|issn=1573-0778|pmc=2780543|pmid=19642007}}</ref> Benzoic acid therefore might have a role in benzotrichloride carcinogenicity, but benzotrichloride has more carcinogenic potential than benzoic acid, suggesting that an intermediate in [[hydrolysis]] is responsible for at least part of the carcinogenicity.<ref name="Yasuo 143–150"/> Research showed that the mutagenicity was not caused by [[Reactive oxygen species|reactive oxygen species (ROS)]] increase, but it did not elucidate what metabolite was the main carcinogen.<ref>{{Cite journal|last1=Yamamoto|first1=Kimiyo N.|last2=Hirota|first2=Kouji|last3=Kono|first3=Koichi|last4=Takeda|first4=Shunichi|last5=Sakamuru|first5=Srilatha|last6=Xia|first6=Menghang|last7=Huang|first7=Ruili|last8=Austin|first8=Christopher P.|last9=Witt|first9=Kristine L.|last10=Tice|first10=Raymond R.|date=2011|title=Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair-deficient chicken DT40 cell lines|journal=Environmental and Molecular Mutagenesis|language=en|volume=52|issue=7|pages=547–561|doi=10.1002/em.20656|issn=1098-2280|pmc=3278799|pmid=21538559}}</ref>

{{reflist}}

[[Category:Trichloromethyl compounds]]

[[Category:Benzene derivatives]]