GLYCIDOL

1. Exposure Data

1.1 Chemical and physical data

1.1.1 Nomenclature

Chem. Abstr. Serv. Reg. No.: 556-52-5

Deleted CAS Reg. Nos: 61915-27-3; 98913-54-3

Chem. Abstr. Name: Oxiranemethanol

IUPAC Systematic Name: 2,3-Epoxypropan-1-ol

Synonyms: Allyl alcohol oxide; epihydrin alcohol; 1,2-epoxy-3-hydroxypropane;

2,3-epoxy-1-propanol; (±)-2,3-epoxy-1-propanol; glycide; (±)-glycidol; (RS)-

glycidol; dl-glycidol; glycidyl alcohol; hydroxy-1,2-epoxypropane; 1-hydroxy-2,3-

epoxypropane; 2-(hydroxymethyl)oxirane; 3-hydroxypropylene oxide; oxiranylmethanol; racemic glycidol

1.1.2 Structural and molecular formulae and relative molecular mass

C3H6O2 Relative molecular mass: 74.08

1.1.3 Chemical and physical properties of the pure substance

(a) Description: Colourless, odourless liquid (Sienel et al., 1987)

(b) Boiling-point: 162 °C (decomposes) (Verschueren, 1996)

(c) Melting-point: –54 °C (Verschueren, 1996)

(d) Density: 1.143 g/cm3 at 25 °C (Lide & Milne, 1996)

(e) Spectroscopy data: Infrared (prism [15765]; grating [28381]), nuclear magnetic

resonance (proton [18790]) and mass spectral data have been reported (Sadtler

Research Laboratories, 1980; Lide & Milne, 1996)

–469–

H2C C CH2 OH

H

O
(f) Solubility: Miscible in all proportions in water, alcohols, ketones, esters, ethers

and aromatics; almost insoluble in aliphatic hydrocarbons (Sienel et al., 1987)

(g) Volatility: Vapour pressure, 120 Pa at 25 °C (American Conference of Governmental Industrial Hygienists, 1999); relative vapour density (air = 1), 2.15

(Verschueren, 1996)

(h) Stability: Flash-point, 71 °C (Sienel et al., 1987); reacts vigorously with strong

caustic soda, strong sulfuric acid and with anhydrous metal halides, such as

stannic and ferric chlorides (Dixie Chemical Co., 1995)

(i) Octanol/water partition coefficient (P): log P, –0.95 (Hansch et al., 1995)

(j) Conversion factor1: mg/m3 = 3.03 × ppm

1.1.4 Technical products and impurities

Glycidol is commercially available with a minimum purity of 95% and a maximum

water content of 1% (Dixie Chemical Co., 1999).

Trade names for glycidol include: Epiol OH.

1.1.5 Analysis

Glycidol can be determined in workplace air by adsorbing the air sample on charcoal, desorbing with tetrahydrofuran and analysing by gas chromatography with flame

ionization detection (Eller, 1994).

1.2 Production

Glycidol is commercially produced by two methods: (1) epoxidation of allyl

alcohol with hydrogen peroxide and a catalyst (tungsten or vanadium); and (2) reaction

of epichlorohydrin with caustic (Grigor’ev et al., 1979; Yoshida & Koyama, 1992;

Richey, 1993; Hutchings et al., 1995).

Information available in 1999 indicated that glycidol was manufactured by two

companies in Japan, and one company each in Germany and the United States

(Chemical Information Services, 1999).

1.3 Use

In 1956, glycidol was only used for research purposes (Hine et al., 1956), but by

1978 it was used in the preparation of glycerol, glycidyl ethers, esters and amines in

the pharmaceutical industry (Proctor & Hughes, 1978) and as a sterilant in pharmaceuticals (Ivashkiv & Dunham, 1973). 

470 IARC MONOGRAPHS VOLUME 77

1 Calculated from: mg/m3 = (relative molecular mass/24.45) × ppm, assuming a temperature of 25 °C and

a pressure of 101 kPa
Glycidol has become an important intermediate for the production of functional

epoxides. For example, reaction of phosgene with glycidol yields 2,3-epoxypropyl

chloroformate. Reaction of glycidol with isocyanates affords the commercially

important glycidyl urethanes (Sienel et al., 1987). It is used as an intermediate in the

production of pharmaceuticals, as an additive for synthetic hydraulic fluids and as a

reactive diluent in some epoxy resin systems (Hooper et al., 1992; American Conference of Governmental Industrial Hygienists, 1999). It is a stabilizer for natural oils

and vinyl polymers, a dye-levelling agent and a demulsifier (American Conference of

Governmental Industrial Hygienists, 1986).

1.4 Occurrence

1.4.1 Natural occurrence

Glycidol is not known to occur as a natural product.

1.4.2 Occupational exposure

According to the 1981–83 National Occupational Exposure Survey (NOES,

1999), as many as 4900 workers in the United States were potentially exposed to

glycidol (see General Remarks). National estimates of workers potentially exposed in

other countries were not available.

1.4.3 Environmental occurrence

Production of glycidol and its broad applications as an intermediate, as a reactive

diluent in epoxy resins and as a stabilizer and a sterilant may result in its release into

the environment through various waste streams (Ivashkiv & Dunham, 1973; Kaplan

et al., 1982; Nomeir et al., 1995; Department of Health and Human Services, 1999). 

1.5 Regulations and guidelines

Occupational exposure limits and guidelines for glycidol are presented in

Table 1.

2. Studies of Cancer in Humans

No data were available to the Working Group.

GLYCIDOL 471
3. Studies of Cancer in Experimental Animals

3.1 Oral administration

3.1.1 Mouse

Groups of 50 male and 50 female B6C3F1 mice, nine weeks of age, were administered 0, 25 or 50 mg/kg bw of glycidol (94% purity, with the primary impurity, as

determined by gas chromatography, being diglycidyl ether at a concentration of 2.8%,

and 3-methoxy-1,2-propanediol (1.2%), 2,6-dimethanol-1,4-dioxane (1.1%), 3-

chloro-1,2-propanediol (0.4%) and methanol (0.1%) as lesser impurities) in distilled

water by gavage on five days per week for 103 weeks. The survival of female mice at

the high dose was significantly lower after week 101 than in the controls. As shown in

Table 2, there was a significantly increased incidence of Harderian gland adenomas

472 IARC MONOGRAPHS VOLUME 77

Table 1. Occupational exposure limits and guidelines for glycidola

Country Year Concentration

(mg/ m3

)

Interpretationb

Australia 1993 75 TWA

Belgium 1993 75 TWA

Denmark 1993 1 STEL

Finland 1998 150 (sk)

225

TWA

STEL

France 1993 75 TWA

Germany 1999 150 TWA

Ireland 1997 75 TWA

Netherlands 1997 150 TWA

Philippines 1993 150 TWA

Russian Federation 1993 5 STEL

Switzerland 1993 75

150

TWA

STEL

Turkey 1993 150 TWA

United States

 ACGIH

 NIOSH

 OSHA

1999

1999

1999

 6.1 (A3)c

 75

150

TWA

TWA

TWA

a From Finnish Ministry of Social Affairs and Health (1998); American Conference of

Governmental Industrial Hygienists (ACGIH) (1999); Deutsche Forschungsgemeinschaft (1999); Occupational Safety and Health Administration (OSHA) (1999)

b TWA, time-weighted average; STEL, short-term exposure limit; A3, confirmed animal

carcinogen with unknown relevance to humans; sk, skin notation

c These countries follow the recommendations of the ACGIH threshold limit values:

Bulgaria, Colombia, Jordan, Republic of Korea, New Zealand, Singapore and Viet Nam
Table 2. Incidence of primary tumours in B6C3F1 mice exposed to glycidol

Animals with tumoursMales Females

Tumour site

0 mg/kg bw 25 mg/kg bw 50 mg/kg bw 0 mg/kg bw 25 mg/kg bw 50 mg/kg bw

Harderian glanda 8/46 12/41 22/44*** 4/46 11/43* 17/43***Forestomachb 0/50 2/50 9/50*** 3/50 5/50 4/50Liverc 24/50 31/50 35/50** 9/50 7/50 14/50Mammary glandd 1/50 5/50 15/50***Lunge 13/50 11/50 21/50* 3/50 4/50 5/50Skinb 0/50 0/50 4/50* – – –Subcutisf 11/50 3/50 4/50 0/50 3/50 9/50***Uterusg – – – 0/50 3/50 3/50

From Irwin et al. (1996)bw, body weighta Adenomas and adenocarcinomasb Squamous-cell papillomasc Hepatocellular adenomas and carcinomasd Adenocarcinomase Alveolar/bronchiolar adenomas or carcinomasf Sarcomas and fibrosarcomasg Carcinomas and adenocarcinomas* p ≤ 0.05; Fisher’s exact test or incidental tumour test**

p ≤ 0.01; Fisher’s exact test

***

p ≤ 0.001; Fisher’s exact test
and adenocarcinomas combined in the high-dose males and in the high- and mid-dose

females, and of Harderian gland adenocarcinomas in the high-dose males. In male

mice only, the incidences of adenomas and carcinomas of the liver, squamous-cell

papillomas of the forestomach and skin and alveolar/bronchiolar adenomas of the lung

were significantly increased at the high dose; in females only, the incidences of

mammary gland adenocarcinomas and of subcutaneous sarcomas and fibrosarcomas

combined were significantly increased at the high dose. There was also a slight

increase in uterine glandular carcinomas in female mice (National Toxicology Program, 1990; Irwin et al., 1996).

3.1.2 Rat

Groups of 50 male and 50 female Fischer 344 rats, eight weeks of age, were administered 0, 37.5 or 75 mg/kg bw of glycidol (purity, 94%, with the main impurities being

those listed in Section 3.1.1) in distilled water by gavage on five days per week for 103

weeks. Survival of rats was significantly lower in the treated groups in both males and

females than in the control groups, with the mean survival being 92, 82 and 66 weeks

for the control, mid- and high-dose males, respectively, and 97, 85 and 78 weeks for the

female dose groups. As shown in Table 3, there was a statistically significant increase in

the incidence of mesotheliomas of the tunica vaginalis/peritoneum in males at both 37.5

and 75 mg/kg bw. There was a statistically significant increase in the incidence of

fibroadenoma and adenocarcinoma of the mammary gland in female rats, and of

mammary fibroadenoma in male rats at both doses in each case. The incidences in the

forestomach of squamous-cell papilloma and of squamous papilloma or carcinoma

combined were significantly increased in female rats at both doses and in male rats at

the high dose. Gliomas of the brain were significantly increased in both sexes at the high

dose. Other tumour types with increased incidence included squamous-cell papillomas

or carcinomas of the mouth or tongue, adenomas or carcinomas of the clitoral gland and

leukaemia in female rats; and Zymbal gland carcinomas, thyroid follicular-cell

adenomas or carcinomas, skin tumours and adenomatous polyps or adenocarcinomas of

the intestine combined in male rats (National Toxicology Program, 1990; Irwin et al.,

1996).

3.1.3 Hamster

Groups of 20 male and 20 female Syrian golden hamsters, 10 weeks of age, were

administered 0.2 mL glycidol solution (96% purity with ‘varying amounts of

polymer’) in a 1:1 mixture of ethyl acetate and corn oil, representing a dose of 12 mg

glycidol (approximately 100 mg/kg bw) by gavage twice a week for 60 weeks. This

was calculated to amount to a total dose of 1.45 g per animal. Groups of 12 male and

12 female hamsters given 0.2 mL ethyl acetate:corn oil for 90 weeks comprised the

controls. Survival was similar among the groups, with the median week of death being

474 IARC MONOGRAPHS VOLUME 77
Table 3. Incidence of primary tumours in Fischer 344/N rats exposed to glycidol

Animal with tumoursaMales Females

Site/tumour

0 mg/kg bw 37.5 mg/kg bw 75 mg/kg bw 0 mg/kg bw 37.5 mg/kg bw 75 mg/kg 

Tunica vaginalis/peritoneumb 3/49 34/50*** 39/47*** – – –Brainc 0/46 5/50* 6/30** 0/49 4/46* 4/46**Clitoral glandd – – – 5/49 9/47 12/45*Forestomache 1/46 2/50 6/32* 0/47 4/38* 11/30***Haematopoietic systemf 25/50 33/50 21/50 13/49 14/44 20/41*Intestineg 0/47 1/50 4/37* – – –Mammary glandh 3/45 8/39 7/17** 14/50 34/50*** 37/50***Mouth/tonguei 3/50 2/50 5/50 1/46 3/37 7/26**Skinj 0/45 5/41* 4/18* – – –Thyroid glandk 1/46 4/42 6/19** 0/50 1/50 3/49Zymbal’s glandl 1/49 3/50 6/48* – – –From Irwin et al. (1996) a Effective numbers (number of animals with tumours among the number of animals surviving at the appearance of the first tumour)b Mesotheliomasc Gliomasd Adenomas and carcinomase Squamous-cell papillomas and carcinomasf Leukaemiag Adenomatous polyps and adenocarcinomash Fibroadenomas and adenocarcinomasi Sebaceous gland adenomas and carcinomas or basal-cell tumoursj Follicular-cell adenomas and carcinomask Carcinomas

* p

≤ 0.05; Fisher’s exact test or incidental tumour test

** 

p

≤ 0.01; Fisher’s exact test

*** 

p

≤ 0.001; Fisher’s exact test
97, 92, 84 and 84 for control males, treated males, control females and treated females,

respectively. There was no statistically significant increase in the incidence of tumours

in any target organ. However, 2/19 males and 4/20 females had haemangiosarcomas

of the spleen compared with 0/12 male and 0/12 female controls (Lijinsky & Kovatch,

1992).

3.2 Skin application

3.2.1 Mouse

A group of 20 female ICR/Ha Swiss mice, eight weeks of age, was administered

glycidol (commercial grade purified by distillation under vacuum) by skin painting

onto the dorsal skin three times per week for 520 days at a concentration of 5% in

acetone. Control groups of 100 female mice of the same strain each included three

100% acetone-treatment and three no-treatment groups, with the vehicle administered

in the same way. Survival was similar between groups. Under this regimen, glycidol

did not induce skin damage or skin tumours (Van Duuren et al., 1967).

4. Other Data Relevant to an Evaluation of Carcinogenicity

and its Mechanisms

4.1 Absorption, distribution, metabolism and excretion

4.1.1 Humans

No data were available to the Working Group.

4.1.2 Experimental systems

Glycidol is rapidly hydrolysed to glycerol (97.2%) and α-chlorohydrin (3-chloro1,2-propanediol, 2.8%) in 0.1 M hydrochloric acid, with a half-life of 10 min. At pH

7 or 8, glycidol readily reacts with glutathione to form S-(2,3-dihydroxypropyl)glutathione (Jones, 1975).

Approximately 87–92% of 37.5 or 75 mg/kg body weight (bw) orally administered

glycidol is absorbed from the gastrointestinal tract of male Fischer 344 rats. Seven to

eight per cent of the dose remained in tissues 72 h following administration. The

highest concentrations of radioactivity were observed in blood cells, thyroid, liver,

kidney and spleen (Nomeir et al., 1995).

S-(2,3-Dihydroxypropyl)glutathione, S-(2,3-dihydroxypropyl)cysteine and β-chlorolactic acid are the major metabolites isolated from rat urine after intraperitoneal administration of glycidol. The generation of β-chlorolactic acid is presumably a result of

initial formation of α-chlorohydrin, with subsequent oxidation by alcohol and aldehyde

476 IARC MONOGRAPHS VOLUME 77
dehydrogenases. Glycidol is hydrolysed to glycerol by rat liver microsomal preparations

(Jones, 1975; Jones & O’Brien, 1980; Patel et al., 1983). 

A single dose by gavage of 500 μL/kg [560 mg/kg] bw glycidol to male Wistar rats

led to significant decreases in hepatic glutathione content between 30 min and 12 h

after treatment. Recovery was complete by 24 h. The decrease in glutathione content

2 h after dosing with 750 μL/kg [840 mg/kg] bw was no greater than that observed after

dosing with 150 μL/kg [168 mg/kg] bw (Montaldo et al., 1984). 

4.2 Toxic effects

4.2.1 Humans

No data were available to the Working Group.

4.2.2 Experimental systems

No histopathological or serum enzyme signs of liver damage were observed in male

Wistar rats dosed by gavage with up to 750 μL/kg [840 mg/kg] bw glycidol (Montaldo

et al., 1984).

4.3 Reproductive and developmental effects

4.3.1 Humans

No data were available to the Working Group.

4.3.2 Experimental systems

Groups of 30–37 pregnant CD-1 mice were treated with glycidol by gavage at

dose levels of 0, 100, 150 or 200 mg/kg bw per day on days 6–15 of gestation, and

then killed on day 18 of gestation. Five of the 30 dams died in the highest-dose group.

There was no reduction in the total number of implantations and no increase in the

numbers of resorptions or fetal deaths per pregnancy, or morphological variations that

could be directly attributed to the treatment. In the highest-dose group, one litter

consisted of 15 stunted fetuses, among which six had cleft palates. However, all 15

stunted fetuses were attributable to a single dam (Marks et al., 1982).

Groups of pregnant Sprague-Dawley rats [numbers not specified] were laparotomized on day 13 of gestation and the embryos of one uterine horn were given intraamniotic injections of glycidol in 0.9% sodium chloride at dose levels of 10, 100 and

1000 μg per fetus. The contrauterine horn embryos received intra-amniotic injections of

0.9% sodium chloride. The dams were killed on day 20 of gestation. Throughout the

treated groups, there was an approximately 50% resorption frequency. No malformed

fetuses were observed in the saline-treated uterine horns or in the glycidol-treated horns

GLYCIDOL 477
at the lower doses, but 44% of the surviving fetuses treated with 1000 μg glycidol were

malformed. The commonest malformations were of the forelimbs (39%), hindlimbs

(22%) and pinnae (11%) (Slott & Hales, 1985).

Adult male and female mice [strain not specified] were mated for 30 min and then

groups of 23–31 females were treated with glycidol [route not stated] at dose levels of

0 or 250 mg/kg bw. The glycidol treatment was given at 1, 6, 9 or 25 h after mating and

the mice were killed on gestational day 17. Resorptions were increased by glycidol

treatment, from 3.2% in the controls to 11.6%, 15.0%, 10.6% and 7.9% in the 1-, 6-, 9-

and 25-h treatment time groups, respectively. Late deaths and anomalies were also

increased in the 1- and 6-h treatment time groups (Rutledge et al., 1992). 

Groups of 34 female (SEC × C57BL6)F1 mice were injected intraperitoneally once

with 0 or 300 mg/kg bw glycidol and then mated the following morning with untreated

(C3H/R1 × C57BL10)F1 males. Newborn mice were looked for in the breeding cages

beginning 18 days after pairing, and were counted and killed. This procedure was

continued through 17 breeding intervals (approximately 347 days). There was no

significant difference in the numbers of offspring per female between the treated

(143.4) and control (147.8) groups (Bishop et al., 1997). 

4.4 Genetic and related effects

4.4.1 Humans

No data were available to the Working Group.

4.4.2 Experimental systems (see Table 4 for references)

The genetic toxicity of glycidol has been reviewed (Ehrenberg & Hussain, 1981).

Glycidol gave a positive response in assays of prophage induction and SOS repair

in Escherichia coli. Results were uniformly positive in several Salmonella typhimurium

reverse mutation assays and in two fungal mutation assays. The sex-linked recessive

lethal mutation assay and the heritable translocation test in Drosophila melanogaster

also gave positive results.

In mammalian assays, glycidol has been tested in human lymphocytes and Chinese

hamster cells in vitro for induction of chromosomal aberrations and sister chromatid

exchanges. It was also tested in vivo in the mouse micronucleus assay. All test results

were positive, as were those of gene mutation assays using Chinese hamster V79 cells

and mouse lymphoma L5178Y cells. An in-vivo assay to detect chromosomal aberrations in mouse bone-marrow cells gave negative results.

The only mammalian assay to give no response without exogenous metabolism was

an unscheduled DNA synthesis test using human cells. This test did, however, give a

positive response in the presence of S9, which was also in contrast to the majority of

the tests, in which the addition of an exogenous metabolizing system reduced the activity of the compound. 

478 IARC MONOGRAPHS VOLUME 77
Table 4. Genetic and related effects of glycidol

Resulta Test system

Withoutexogenousmetabolicsystem

Withexogenousmetabolicsystem

Doseb

(LED or HID)

Reference

Prophage induction, SOS repair test, DNA strand breaks,

cross-links or related damage

– NT 500 μg/plate Mamber et al. (1

Escherichia coli PQ37, SOS chromotest + NT 244.5 von der Hude et Escherichia coli pol A/W3110-p3478, differential toxicity

(liquid suspension test)

+ NT 430 μg/well McCarroll et al. 

Escherichia coli WP2/WP100 rec assay, differential toxicity + NT 54 μg/well McCarroll et al. 

Escherichia coli WP2/WP100 rec assay, differential toxicity + NT 10 000 μg/plate Mamber et al. (1

Salmonella typhimurium TA100, reverse mutation + NT 100 μg/plate Wade et al. (197

Salmonella typhimurium TA100, reverse mutation + + 61.7 μg/plate Thompson et al. Salmonella typhimurium TA100, reverse mutation + + 33 μg/plate Canter et al. (19

Salmonella typhimurium TA100, reverse mutation + NT 25 μg/plate Claxton et al. (1

Salmonella typhimurium TA1535, reverse mutation + + 20.6 μg/plate Thompson et al. Salmonella typhimurium TA1535, reverse mutation + + 500 μg/plate Mamber et al. (1

Salmonella typhimurium TA1535, reverse mutation + + 3 μg/plate Canter et al. (19

Salmonella typhimurium TA1537, reverse mutation (+) + 1670 μg/plate National Toxico

Program (1990)

Salmonella typhimurium TA98, reverse mutation (spot test) – NT 10 000 μg/plate Wade et al. (197Salmonella typhimurium TA98, reverse mutation + + 3333 μg/plate National Toxico

Program (1990)

Salmonella typhimurium TA97, reverse mutation + + 333 μg/plate National Toxico

Program (1990)

Escherichia coli (Sd-4), reverse mutation + NT 740 Hussain (1984)Klebsiella pneumoniae, forward mutation + NT 14.8 Voogd et al. (19

Schizosaccharomyces pombe, forward mutation + + 74 Migliore et al. (1Neurospora crassa, reverse mutation + NT 37 000c (15 min) Kolmark & Gile

Drosophila melanogaster, sex-linked recessive lethal mutations + 1230 in feed Foureman et al. 
Table 4 (contd) Resulta Test system Without exogenous metabolic system With exogenous metabolic system Doseb (LED or HID) Reference Drosophila melanogaster, heritable translocation test + 1230 in feed Foureman et al. (Gene mutation, Chinese hamster lung V79 cells, 6-thioguanine resistance in vitro + NT 0.15 Smith et al. (199

Gene mutation, mouse lymphoma L5178Y cells, Tk locus in vitro + + 8 Thompson et al. 

Gene mutation, mouse lymphoma L5178Y cells, Tk locus in vitro + NT 1.43 National Toxicol

Program (1990) Sister chromatid exchange, Chinese hamster cells in vitro + + 1.11 National ToxicolProgram (1990) Sister chromatid exchange, Chinese hamster V79 cells in vitro + NT 92.6 von der Hude et 

Chromosomal aberrations, Chinese hamster cells in vitro + + 12.5 National Toxicol

Program (1990) Sister chromatid exchange, human lymphocytes in vitro + NT 3.7 Norppa et al. (19

Chromosomal aberrations, human lymphocytes in vitro + NT 29.6 Norppa et al. (19

Micronucleus formation, B6C3F1 mice in vivo + 150 ip × 2 National Toxicol

Program (1990)

Chromosomal aberrations, mouse bone-marrow cells in vivo – 226 po × 5 Thompson & HilChromosomal aberrations, mouse bone-marrow cells in vivo – 145 ip × 5 Thompson & Hil

a +, positive; –, negative; NT, not testedb LED, lowest effective dose; HID, highest ineffective dose; in-vitro tests, μg/mL; in-vivo tests, mg/kg bw/day; Drosophila tests, ppm; pintraperitonealc One dose tested; time-dependent response
Glycidol has been demonstrated to alkylate DNA in a number of in-vitro studies

(Hemminki, 1979, Hemminki et al., 1980; Hemminki, 1983; Djuric & Sinsheimer,

1984a,b; Djuric et al., 1986; Segal et al., 1990).

4.5 Mechanistic considerations

Glycidol possesses a reactive epoxide moiety. This is likely to be responsible for

the genotoxic activity of the compound without a requirement for metabolic activation.

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Glycidol is an epoxide used as a chemical intermediate in the production of

functional epoxides, glycidyl urethanes, pharmaceuticals and other products. It is also

used as a reactive diluent in epoxy resin systems and as a sterilant. Occupational

exposure may occur during its production and use. No data were available on environmental exposure to glycidol.

5.2 Human carcinogenicity data

No data were available to the Working Group.

5.3 Animal carcinogenicity data

Glycidol has been tested by oral administration in one study in mice, in one study

in rats and in one study in hamsters. It was also tested by skin application in one study

in mice. After oral administration to mice, it produced increases in tumours of the

Harderian gland in both males and females, of the forestomach, lung, liver and skin in

males, and of the mammary gland and subcutaneous tissue in females. In rats, it

produced increases in the incidence of gliomas of the brain and forestomach tumours

in both males and females. Mesotheliomas of the tunica vaginalis/peritoneum, as well

as tumours of the intestine, skin, thyroid gland and Zymbal gland were increased in

males. Tumours of the clitoral gland, mammary gland and oral mucosa as well as

leukaemia were increased in females. 

In hamsters, there was a marginal increase in the incidence of splenic haemangiosarcomas after oral administration.

No skin tumours were observed in mice after skin application.

GLYCIDOL 481
5.4 Other relevant data

Glycidol is an alkylating agent which reacts readily with glutathione. It causes a

decrease in glutathione content in rat liver, probably reflecting its binding to glutathione. In rats, it is metabolized to oxidative and glutathione-derived products. No

toxicokinetic data on humans were available.

No data on developmental and reproductive effects in humans were available to

the Working Group.

No effects on fertility or development were observed in mice given intraperitoneal

injections of glycidol 24 h before mating or orally during organogenesis. In contrast,

when a single dose of glycidol was administered to female mice within 25 h after

mating, the numbers of fetal deaths and anomalies were increased. Intra-amniotic

injection of glycidol on day 13 of gestation in rats increased the frequency of

resorptions and, at high doses, limb malformations.

Glycidol has been shown to be genotoxic using assays covering a wide range of

end-points. In vitro, it did not require metabolic activation to elicit positive responses.

5.5 Evaluation

No epidemiological data relevant to the carcinogenicity of glycidol were available.

There is sufficient evidence in experimental animals for the carcinogenicity of

glycidol.

Overall evaluation

Glycidol is probably carcinogenic to humans (Group 2A).

In making the overall evaluation, the Working Group took into consideration that

glycidol is a direct-acting alkylating agent that is mutagenic in a wide range of in-vivo

and in-vitro test systems.

6. References

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Threshold Limit Values and Biological Exposure Indices, 5th Ed., Cincinnati, OH, ACGIH®,

p. 287

American Conference of Governmental Industrial Hygienists (1999) TLVs and other Occupational Exposure Values—1999 CD-ROM, Cincinnati, OH, ACGIH®

Bishop, J.B., Morris, R.W., Seely, J.C., Hughes, L.A., Cain, K.T. & Generoso, W.M. (1997)

Alterations in the reproductive patterns of female mice exposed to xenobiotics. Fundam.

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482 IARC MONOGRAPHS VOLUME 77
Canter, D.A., Zeiger, E., Haworth, S., Lawlor, T., Mortelmans, K. & Speck, W. (1986) Comparative mutagenicity of aliphatic epoxides in Salmonella. Mutat. Res., 172, 105–138

Chemical Information Services (1999) Directory of World Chemical Producers, Version 99.1.0

[CD-ROM], Dallas, TX 

Claxton, L.D., Houk, V.S., Monteith, L.G., Myers, L.E. & Hughes, T.J. (1991) Assessing the

use of known mutagens to calibrate the Salmonella typhimurium mutagenicity assay:

I. Without exogenous activation. Mutat. Res., 253, 137–147

De Flora, S. (1981) Study of 106 organic and inorganic compounds in the Salmonella/microsome test. Carcinogenesis, 2, 283–298

De Flora, S., Zanacchi, P., Camoirano, A., Bennicelli, C. & Badolati, G.S. (1984) Genotoxic

activity and potency of 135 compounds in the Ames reversion test and in a bacterial DNArepair test. Mutat. Res., 133, 161–198

Department of Health and Human Services (1999) 8th Report on Carcinogens. 1998 Summary,

Research Triangle Park, NC, National Toxicology Program, pp. 129–130

Deutsche Forschungsgemeinschaft (1999) List of MAK and BAT Values. Report No. 35,

Weinheim, Wiley-VCH, p. 62

Dixie Chemical Co. (1995) Product Technical Bulletin: 2,3-Epoxy-1-propanol (Glycidol),

Houston, TX 

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