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0050

Epichlorohydrin; CASRN 106-89-8

Health assessment information on a chemical substance is included in IRIS only after a 

comprehensive review of chronic toxicity data by U.S. EPA health scientists from several 

Program Offices and the Office of Research and Development. The summaries presented in 

Sections I and II represent a consensus reached in the review process. Background 

information and explanations of the methods used to derive the values given in IRIS are 

provided in the Background Documents. 

STATUS OF DATA FOR Epichlorohydrin 

File First On-Line 01/31/1987

_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects 

_I.A. Reference Dose for Chronic Oral Exposure (RfD) 

Substance Name — Epichlorohydrin 

CASRN — 106-89-8 

The Oral RfD for this substance has been withdrawn pending further review by the RfD/RfC 

Work Group. 

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

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Reference Dose for Chronic Oral Exposure (RfD)

Category (section) Status Last Revised

Oral RfD Assessment (I.A.) withdrawn 04/01/1992 

Inhalation RfC Assessment (I.B.) on-line 04/01/1992

Carcinogenicity Assessment (II.) on-line 02/01/1994 

Integrated Risk Information System

http://www.epa.gov/iris/subst/0050.htm

Last updated on Monday, March 07, 2011

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contractor of the more recent toxicology literature pertinent to the RfD for Epichlorohydrin 

conducted in September 2002 identified one or more significant new studies. IRIS users may 

request the references for those studies from the IRIS Hotline at hotline.iris@epa.gov or 

(202)566-1676. 

EPA Contacts: 

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in 

general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet 

address). 

_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC) 

Substance Name — Epichlorohydrin 

CASRN — 106-89-8 

Last Revised — 04/01/1992 

The inhalation Reference Concentration (RfC) is analogous to the oral RfD and is likewise 

based on the assumption that thresholds exist for certain toxic effects such as cellular 

necrosis. The inhalation RfC considers toxic effects for both the respiratory system (portal-ofentry) and for effects peripheral to the respiratory system (extrarespiratory effects). It is 

expressed in units of mg/cu.m. In general, the RfC is an estimate (with uncertainty spanning 

perhaps an order of magnitude) of a daily inhalation exposure of the human population 

(including sensitive subgroups) that is likely to be without an appreciable risk of deleterious 

effects during a lifetime. Inhalation RfCs were derived according to the Interim Methods for 

Development of Inhalation Reference Doses (EPA/600/8-88/066F August 1989) and 

subsequently, according to Methods for Derivation of Inhalation Reference Concentrations 

and Application of Inhalation Dosimetry (EPA/600/8-90/066F October 1994). RfCs can also 

be derived for the noncarcinogenic health effects of substances that are carcinogens. 

Therefore, it is essential to refer to other sources of information concerning the 

carcinogenicity of this substance. If the U.S. EPA has evaluated this substance for potential 

human carcinogenicity, a summary of that evaluation will be contained in Section II of this 

file. 

__I.B.1. Inhalation RfC Summary 

*Conversion Factors: MW = 92.53. Assuming 25 degrees C and 760 mmHg, NOAEL (mg/cu.m) = 5 ppm x 92.53/24.45 

= 19 mg/cu.m. NOAEL(ADJ) = NOAEL (mg/cu.m) x 6 hours/24 hours x 5 days/7 days = 3.4 mg/cu.m. The NOAEL

(HEC) was calculated for a gas:respiratory effect in the extrathoracic region. MVa (subchronic, female F344 rat) = 0.14 

Critical Effect Exposures* UF MF RfC 

Changes in the 

nasal turbinates 

Rat and Mouse 

90-Day Inhalation 

Study 

Quast et al., 1979a 

NOAEL: 19 mg/cu.m (5 ppm) 

NOAEL(ADJ): 3.4 mg/cu.m 

NOAEL(HEC): 0.36 mg/cu.m 

LOAEL: 95 mg/cu.m (25 ppm) 

LOAEL(ADJ): 17 mg/cu.m 

LOAEL(HEC): 1.82 mg/cu.m 

300 1 1E-3 

mg/cu.m 

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cu.m/day, MVh = 20 cu.m/day, Sa(ET) = 11.6 sq.cm, Sh(ET) = 177 sq.cm. RGDR = (MVa/Sa)/(MVh/Sh) = 0.107. 

NOAEL(HEC) = 3.4 x RGDR = 0.36 mg/cu.m. 

__I.B.2. Principal and Supporting Studies (Inhalation RfC) 

Quast, J.F., J.W. Henck, B.J. Postma, D.J. Schuetz and M.J. McKenna. 1979a. Epichlorohydrin 

- subchronic studies I. A 90-Day Inhalation Study in Laboratory Rodents. 8D Submission. 

Microfiche No. 206200. 

In a 3-month study, groups of B6C3F1 mice, Fischer 344 rats, and Sprague- Dawley rats 

(10/sex/concentration/strain) were exposed to 0, 5, 25, or 50 ppm (0, 19, 95, or 189 

mg/cu.m) epichlorohydrin (99.8% purity), 6 hours/day, 5 days/week (duration-adjusted to 

3.4, 17, and 34 mg/cu.m, respectively), for 61-62 exposures. Epichlorohydrin vapor was 

generated by metering the liquid into a warmed vaporization flask then passed through the 

chamber airflow with compressed air. The dynamic airflow conditions were maintained at 70-

75 degrees F and relative humidity at 40-60%. Animals were observed for clinical signs of 

toxicity and measured biweekly for body weight changes. Clinical chemistry, hematology, and 

urinalysis were conducted; organ weights were obtained; and gross and histological 

examination of all tissues, including lungs, nasal turbinates (3-4 sections), liver, kidney, and 

male reproductive organs was conducted. Animals were sacrificed at 1 month and 3 months 

(10/concentration) and all parameters were evaluated except that histological observations 

were made on only five animals per concentration in the control and 50-ppm animals at the 

interim sacrifice. At the 3-month terminal sacrifice, animals in all groups were evaluated for 

histopathological effects of the respiratory system, liver, and kidney; other tissues were 

examined only in the control and 50-ppm groups. 

In rats, epichlorohydrin-related effects in the respiratory epithelium of the nasal turbinates 

(i.e., inflammation, focal erosions, hyperplasia, and metaplasia), were reported in 25- and 

50-ppm F344 rats (males, 9/10, 10/10; females, 8/10, 10/10, respectively) and SpragueDawley rats (males, 9/10, 10/10; females, 10/10, 10/10, respectively). This effect was 

observed in all exposed rats in the 50-ppm group examined at the 1-month interim sacrifice 

and in none of the controls at 1 or 3 months or in the 5-ppm group at 3 months. Focal effects 

in the olfactory epithelium and suppurative inflammatory exudate were also observed in male 

and female rats of both strains after exposure to 50 ppm. Inflammation of the pulmonary 

region described as mononuclear cell infiltrates or focal pneumonitis was observed in most of 

the control and exposed rats of both strains, making conclusions about possible effects in the 

pulmonary region impossible. Inflammation of the nasal turbinates (described as focal 

subepithelial mononuclear cell infiltrate) was observed in most rats of both strains in the 

control and 5 ppm groups but not in the 25- and 50-ppm groups. This lesion indicates an 

underlying inflammatory reaction in these tissues which is not exposure-related. However, 

the location of this lesion makes it distinct from the epithelial effects observed in the rats 

exposed to higher concentrations. At the 1- and 3-month sacrifices, the 50-ppm groups in 

both rat strains (except for the Sprague-Dawley males killed at 3 months) exhibited 

significant increases (p<0.05) in the relative kidney weight compared with controls. Slight 

increased kidney effects (e.g., dilated tubules, swollen appearance) were also exhibited in 

female rats exposed to 50 ppm. No other treatment-related effects were observed. The 

NOAEL of 5 ppm epichlorohydrin was determined for nasal turbinate injury [rat NOAEL(HEC) 

values range from 0.36 for female F344 to 0.70 for male Sprague-Dawley (SD), due to 

differences in ventilation volume; RGDR = 0.107 - 0.206 based on respiratory effects in the 

extrathoracic region]. A NOAEL for kidney effects is identified at 25 ppm [NOAEL(HEC) = 17 

mg/cu.m]. The respiratory effects in rats are used for derivation of the RfC because of the 

greater severity of the lesion in rats, the involvement of respiratory and olfactory epithelium, 

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and the lower calculated NOAEL(HEC). 

Results in mice after 3 months showed focal erosion, hyperplasia, and metaplasia in the 

respiratory epithelium of the nasal turbinates in 0/10, 0/9, 8/8, and 10/10 males and in 0/9, 

0/9, 10/10, and 9/9 females of the 0, 5-, 25-, and 50-ppm groups, respectively. This finding 

was also reported in 4/5 males and 5/5 females in the 50-ppm group compared with 0/10 in 

the controls at the 30-day sacrifice. Suppurative inflammatory exudate or mucus in the 

lumen of the nasal turbinates were reported in 7 males and 7 females in the highconcentration group. Focal effects in the olfactory epithelium were reported in only one 

female in the 50-ppm group. There were no other clearly exposure- related effects observed. 

However, 2, 1, 0, and 0 males and 9, 9, 0, and 0 females in the control, 5-, 25-, and 50-ppm 

groups, respectively, exhibited focal subepithelial mononuclear cell infiltrate in the nasal 

turbinates. This lesion indicates an underlying inflammatory reaction in these tissues that is 

not exposure-related. However, the location of this lesion makes it distinct from the epithelial 

effects in the groups exposed to higher concentrations. Inflammatory reactions in the 

tracheobronchiolar and pulmonary region, which may have been treatment related, were 

observed in a few animals in the high- concentration groups. All other microscopic findings 

were interpreted to be spontaneous. There was no indication that the investigators tested for 

viral infection. A NOAEL of 5 ppm was established for changes in the nasal turbinates of mice 

(HEC = 0.41 mg/cu.m, based on respiratory tract effects in the extrathoracic region in 

females). The HEC for nasal effects is essentially identical in rats and mice. The lesser 

severity of the lesion in mice may be due to their ability to reduce their ventilation in 

response to an irritant to a greater extent than rats (see discussion of Kane et al., 1979). 

Mice have previously shown an ability to decrease their minute volume by up to 75% as 

compared with a maximal 45% reduction in rats when exposed to formaldehyde (Barrow et 

al., 1983; Chang et al., 1983). This study supports the finding of nasal effects at 25 and 50 

ppm in rats. 

__I.B.3. Uncertainty and Modifying Factors (Inhalation RfC) 

UF — An uncertainty factor of 300 reflects a factor of 10 to account for sensitive human 

subpopulations and 3 to account for interspecies extrapolation. An additional factor of 10 was 

applied to account for extrapolation from a subchronic study and for data deficiencies, 

including the lack of a 2-generation reproduction study. 

MF — None 

__I.B.4. Additional Studies/Comments (Inhalation RfC) 

Quast et al. (1979b) conducted a short-term study in Fischer 344 rats, Sprague-Dawley rats, 

and B6C3F1 mice (5/species/sex/ concentration). There were nine exposures of 0 or 100 

ppm (378 mg/cu.m) to epichlorohydrin 7 hours/day, 5 days/week for 12 days. Significant 

decreased body weight gain, thymic atrophy, increased relative kidney weights (rats only), 

and leukocytosis were reported in the 100-ppm exposed animals for both rat strains. 

Degeneration, discoloration, inflammation, and hyperplasia of the nasal turbinates were 

consistently observed to some degree in all exposed animals. These effects were located in 

the respiratory epithelium of mice and in the respiratory and olfactory epithelium of rats. 

Changes in the kidney (e.g., discoloration, tubular nephrosis, dilated tubules, edema), were 

also evident in most of the exposed rats, but were not found in the mice. Like the Quast et 

al. (1979a) study, mononuclear cell infiltrate was evident in the nasal turbinates of the 

control groups of rats and mice. Mononuclear cell infiltrate in the tracheobronchial and 

pulmonary region was observed in most rats (control and exposed) and in slightly more 

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exposed mice than controls. 

Union Carbide (1983) studied groups of 23-32 Wistar rats (sex unspecified) exposed to 68 or 

136 ppm epichlorohydrin (266 or 515 mg/cu.m), 7 hours/day, 5 days/week (durationadjusted to 55 and 107 mg/cu.m), for 45 exposures. Similar groups of rats were exposed to 

0, 5, 8, 17, 21 or 43 ppm epichlorohydrin (19, 30, 64, 80, or 163 mg/cu.m) for 90 or 91 

exposures (duration-adjusted to 4, 6.3, 13, 17, and 34 mg/cu.m). Groups of two hybrid 

Basanji-Cocker dogs and two Rhesus macaque monkeys (sex unspecified) were also exposed 

to epichlorohydrin at 0 or 21 ppm (80 mg/cu.m) for 90 exposures (duration-adjusted to 17 

mg/cu.m). Body weights were measured weekly and clinical chemistry was conducted six 

times during the study. Animals were sacrificed after the last exposure. The kidneys and liver 

were weighed and the tissues examined for histopathological changes. Exposure-related 

deaths occurred in rats exposed at 68 ppm or greater. These animals exhibited lung 

irritation, kidney injury, and weight gain depression. In the rat, a NOAEL of 43 ppm (HEC = 

34 mg/cu.m) was determined for these extrarespiratory effects. In the 21-ppm exposed 

monkeys and dogs, lung effects (e.g., hemosiderin deposits, bronchial irritation, and focal 

proliferation of alveolar septa), and kidney damage (e.g., focal cloudy swelling of the 

proximal convoluted tubules) were described in the study. However, no incidence data or 

statistical significance was provided for these findings. The study was also limited because 

the nasal turbinates were not examined and too few dogs and monkeys were tested. 

In a chronic bioassay, groups of 100 male Sprague-Dawley rats were exposed to 10 or 30 

ppm epichlorohydrin (38 and 114 mg/cu.m, respectively) 6 hours/day, 5 days/week 

(duration-adjusted to 7 and 20 mg/cu.m) for their lifetime (136 weeks) (Laskin et al., 1980). 

The control animals were sham exposed or untreated. Beginning at 40 weeks of exposure, 

significantly decreased body weight was observed in the high-concentration rats. The 

incidences of kidney lesions (e.g., tubular degenerative changes, tubular dilation) at the end 

of the exposure were 14-24, 37, and 65% in animals exposed to 0, 10, and 30 ppm, 

respectively. The authors reported that, qualitatively, the lesions in exposed animals were 

similar to those observed in the controls. The severity of the lesion was stated to be greater 

in the 30-ppm group than in the controls or 10-ppm group. Kidney damage was also 

observed in rats exposed to 100 ppm 6 hours/day for 30 days. No other nonneoplastic effects 

were evident. Severe nasal inflammatory changes (not further specified) were exhibited in 

90% of the control animals and inflammation of the tracheobronchial and pulmonary regions 

of the respiratory tract were also reported, making conclusions about the respiratory effects 

difficult. Details about incidence and severity of lesions were not provided. Because chronic 

inflammation in the bronchial tree and upper respiratory region were reported in the controls 

and exposed animals, exposure-related effects on the respiratory tract could not be 

assessed. Because of the lack of detail in the reporting of the kidney lesion and the high 

control incidence, the 30-ppm group is considered a LOAEL. The NOAEL for kidney effects is 

10 ppm [NOAEL(HEC) = 38 mg/cu.m]. 

Gage (1959) exposed groups of 8 Wistar rats to 9, 17, 27, 56, or 120 ppm epichlorohydrin 

(34, 64, 102, 212, or 454 mg/cu.m) 6 hours/day, 5 days/week for a total of 11-19 

exposures. No controls are reported. No effects were noted at 9 and 17 ppm. Exposure to 27 

ppm resulted in respiratory irritation, but criteria for this judgment were not discussed. 

Lethargy, weight loss, respiratory distress and nasal discharge were observed at 56 ppm, but 

no histological effects were noted in the lungs. Exposure to 120 ppm resulted in congestion 

and edema in the lungs, liver congestion and necrosis, and tubular atrophy in the kidneys. 

Urinary protein excretion was significantly increased. Although inadequately reported, this 

study suggests that high concentration of epichlorohydrin causes peripheral lung effects and 

extrarespiratory effects. 

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Acute exposures (6 hours) to 283-445 ppm epichlorohydrin resulted in severe pulmonary 

edema, hemorrhage, and increased lung-to-body weight ratio (Laskin et al., 1980). 

Kane et al. (1979) exposed male Swiss-Webster mice to a range of epichlorohydrin 

concentrations for 15 minutes and measured the decrease in respiratory frequency. The data 

were plotted as percent decrease in respiratory rate versus the logarithm of the exposure 

concentration, to determine the RD50, the concentration predicted to cause a 50% decline in 

respiratory frequency. The RD50 for epichlorohydrin in this model was 687 ppm. These 

authors suggested that a minimal irritation level for humans is 0.01 times the RD50-6.87 

ppm. In a study designed to evaluate the respiratory lesions resulting from exposure to the 

RD50, Buckley et al. (1984) exposed 20 male Swiss-Webster mice to 697 ppm for 6 hours. 

All exposed mice were found dead or in a moribund condition at the end of the exposure. 

Histopathology of the respiratory tract showed ulceration and necrosis in the respiratory and 

olfactory epithelium of the nose as well as tracheal epithelial exfoliation and hyperplasia and 

slight bronchiolar exfoliation. 

Thirty Sprague-Dawley rats/sex/concentration and 10 male New Zealand white 

rabbits/concentration were exposed to 0, 5, 25, or 50 ppm (19, 95, or 189 mg/cu.m, 

respectively) epichlorohydrin (98.8% purity), 6 hours/day, 5 days/week (duration-adjusted 

to 3.4, 17, and 34 mg/cu.m), for 10 weeks, followed by a 10-week postexposure period 

(John et al., 1979, 1983a). The exposure duration was considered equivalent to one 

spermatogenesis cycle. At the end of the 10-week exposure, 5 rats/sex/concentration and 3-

4 rabbits/concentration were sacrificed. At the end of the postexposure period, 10 

rats/sex/concentration and the remaining rabbits were killed and examined for 

histopathologic changes. Histopathology was performed on an extensive list of tissues 

including kidney, liver, lung, trachea, and four sections of the nose. 

Twenty-five exposed male rats were mated to unexposed females on exposure weeks 2, 4, 7, 

and 10 and postexposure weeks 2, 5, and 10. During mating, exposed males were housed 

with 2 females during the 18 nonexposure hours per day for 7 days. The 25 exposed female 

rats were mated with unexposed males after the 10-week exposure. There was a significant 

reduction in the fertility of the 50-ppm exposed male rats (16, 8, 8, and 12% fertile for 

exposure weeks 2, 4, 7, and 10, respectively). A slight reduction in fertility in the 25-ppm 

exposed male rats was not statistically significant. The average number of implants in 

unexposed females that mated with exposed males was significantly (p<0.005) lower in the 

25-and 50-ppm males during the exposure period. These effects were no longer seen at 2 

weeks post-exposure. No histological changes were seen in the testes in 5 males at the end 

of the exposure or in 10 males at the end of the recovery period. Exposed female rats mated 

at the end of the exposure period showed no effect on estrous pattern, percent pregnant, 

gestation length, litter size, or pup survival at two days. Therefore, a NOAEL of 5 ppm (HEC 

= 3.4 mg/cu.m) was calculated for reproductive toxicity in male rats. 

The high-concentration group showed significantly increased relative kidney weight and focal 

tubular changes in the kidneys. No degeneration or necrosis was observed in the kidney and 

clinical chemistry parameters reflective of kidney function were normal. Degenerative 

changes in the nasal turbinates (e.g., inflammation, focal lesions, and changes in the 

respiratory epithelial region), were seen in the 25- and 50-ppm females and in the 50-ppm 

males after the exposure period. The NOAEL for these respiratory effects is 5 ppm [NOAEL

(HEC) = 0.7 mg/cu.m]. The effects ranged from moderate to severe in the highconcentration group and were similar to the effects described in the principal study. Since 

these findings were not exhibited in animals at the final sacrifice (10 weeks post exposure), 

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the changes in the nasal turbinates were considered reversible. 

In the rabbits, 10 animals per concentration were mated during week 10 of exposure. No 

reproductive effects were noted in rabbits exposed to epichlorohydrin including percent 

fertile; number of implantations; and based on weekly examination, no effect on sperm 

viability, motility, or number. In the 25- and 50-ppm groups, exposed rabbits had bilateral 

suppurative rhinitis or sinusitis and pneumonia compared with controls. The changes in the 

nasal turbinates were not observed at the end of the 10-week recovery period. A NOAEL of 5 

ppm was determined based on inflammation and erosion of the nasal turbinates in the male 

rabbits. Lack of data on the surface area of the respiratory tract in rabbits precludes 

calculation of the HEC. 

The male reproductive effects of epichlorohydrin have been studied in short-term inhalation 

exposures and by other routes of administration. Hahn (1970) reported that male SD rats 

dosed orally with 15 mg/kg/day for 12 days showed loss of fertility within the first week of 

exposure; this effect was reversible within 1 week of the end of exposure. No effects were 

seen on copulatory behavior or on the histopathology of the reproductive organs. Toth et al., 

1989, treated male and female rats orally with 12.5, 25, or 50 mg/kg/day epichlorohydrin for 

21 days (males) or 25, 50, or 100 mg/kg/day (females) for 14 days prior to mating and 

during gestation. Both males and females were mated to unexposed animals and no effects 

were seen on reproduction in exposed females. Male fertility was examined in high-dose 

males only and they were found to be infertile. No effect was observed on copulatory 

behavior, sperm counts, or sperm morphology. Significantly reduced linear velocity and 

curvilinear velocity was observed in exposed animals at 12.5 mg/kg/day and higher, and 

reduced linearity of motion was observed at 50 mg/kg/day. The percent motile sperm was 

reported to be unaffected in this study, but a later reanalysis (Toth et al., 1991) reported this 

parameter to be significantly affected at 25 and 50 mg/kg/day. In a further examination of 

reproductive effects by the inhalation route, Slott et al. (1990) exposed rats to 100 ppm for a 

single 4-hour exposure. No effect was seen on percent motile sperm or sperm counts at 1-14 

days post exposure. Significant decreases were reported in curvilinear and linear velocity at 1 

day post exposure but not at 2-14 days post exposure. 

These studies show a specific effect on sperm motion in rats exposed to epichlorohydrin. This 

effect has been postulated to be mediated through alpha-chlorohydrin, a metabolite of 

epichlorohydrin, which also causes reduced sperm motility through a mechanism thought to 

involve inhibition of sperm glycolytic enzymes. The effects on sperm velocity measured by 

Toth et al. (1989) and Slott et al. (1990) are considered to reflect sperm energy utilization. 

In a study designed to evaluate the correlation between sperm motion parameters and 

fertility measures, Toth et al. (1991) dosed male rats orally with 6.25, 12.5, and 25 

mg/kg/day epichlorohydrin for 23 days. Exposed males were mated with unexposed females 

on days 19 and 22. Fertility was measured as the presence of fertilized ova 18 hours after 

mating, and the number of implants on day 14 of gestation. Both measures of fertility were 

decreased in a dose-dependent fashion by epichlorohydrin exposure, as were several 

measures of sperm motion. A significant correlation was reported between fertility 

parameters and sperm motion parameters. 

Studies of reproductive function in humans occupationally exposed to epichlorohydrin (Milby 

et al., 1981; Milby and Whorton, 1980; Venable et al., 1980) have shown no evidence of 

reduced sperm count in the exposed groups. Detailed measurement of sperm motion has not 

been applied to an occupationally exposed population. 

These reproductive studies indicate that the reproductive toxicity of epichlorohydrin is 

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probably mediated by an effect on mature sperm, and that fertility effects are observed at 

lower epichlorohydrin doses than effects on sperm morphology, production, or testicular 

histology. Histopathology of the reproductive organs has been observed at much higher 

doses by oral and injection routes than doses shown to affect fertility (Cooper et al., 1974; 

Kluwe et al., 1983). The effects show a rapid onset and a rapid and complete reversal after 

exposure ends. 

In a developmental toxicity study by Pilny et al. (1979, also John et al., 1983b), pregnant 

Sprague-Dawley rats (43-46/group) and New Zealand white rabbits (20-25/group) were 

exposed to 0, 2.5, or 25 ppm (0, 9.5, and 95 mg/cu.m) epichlorohydrin, 7 hours/day, on 

gestational days 6-15 or 6-18 for rats and rabbits, respectively. Animals were sacrificed on 

the last day of gestation (day 21 for rats and day 29 for rabbits). Maternal body weight and 

liver weight were recorded and fetuses were examined for external, soft tissue (one-third 

fetuses), and skeletal abnormalities. In the high-concentration rats, maternal weight was 

significantly decreased on days 6, 8, 10, 12, and 16 of gestation. However, maternal weights 

were reported to be significantly less prior to exposure (data not provided in report) so this is 

not a reliable indication of maternal toxicity. In addition, maternal weight gain was not 

significantly reduced except on day 6. Food consumption was significantly lowered on 

gestational days 6-14 while water consumption was increased on gestational days 9-20 in the 

rats. In the 32-36 litters per group examined, there were no significant effects on fetal body 

weight, number of corpora lutea, live fetuses, implantations, resorptions, or malformations. 

In the 16- 23 litters per group of rabbits examined, no effects on maternal toxicity or 

developmental effects were observed. Although the nose, trachea, and lungs were preserved 

at necropsy, no histological observations are reported. This study demonstrates a freestanding NOAEL of 25 ppm (HEC = 95 mg/cu.m) for maternal and developmental toxicity. 

A pharmacokinetic study (Smith et al. 1979) found that 1 and 100 ppm [14C]-

epichlorohydrin inhaled for 6 hours in rats resulted in a 5-fold greater amount of radioactivity 

per tissue mass in the nasal turbinates than the lungs. 

In humans, epichlorohydrin is known to cause respiratory irritation. However, occupational 

studies other than those focused on reproductive effects discussed above have only 

evaluated mortality in workers (Enterline et al., 1990; Tsai et al., 1990). 

__I.B.5. Confidence in the Inhalation RfC 

Study — Medium 

Database — Medium 

RfC — Medium 

The subchronic inhalation study in rats and mice (Quast et al., 1979a) was well conducted 

and contained detailed histopathological examinations of numerous tissues including the 

respiratory tract. However, it was given a medium confidence because of the inflammation in 

the respiratory tract of control and exposed animals. The database is given a medium 

confidence because chronic studies which adequately address the respiratory system and a 

two-generation reproductive study are lacking. The only chronic inhalation study (Laskin et 

al., 1980) is confounded by severe nasal inflammation in the controls. Medium confidence in 

the RfC follows. 

__I.B.6. EPA Documentation and Review of the Inhalation RfC 

Source Document — This assessment is not presented in any existing U.S. EPA document. 

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Other EPA Documentation — U.S. EPA, 1985a,b, 1984 

Agency Work Group Review — 09/19/1989, 12/12/1991 

Verification Date — 12/12/1991 

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

contractor of the more recent toxicology literature pertinent to the RfC for Epichlorohydrin 

conducted in September 2002 identified one or more significant new studies. IRIS users may 

request the references for those studies from the IRIS Hotline at hotline.iris@epa.gov or 

(202)566-1676. 

__I.B.7. EPA Contacts (Inhalation RfC) 

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in 

general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet 

address). 

_II. Carcinogenicity Assessment for Lifetime Exposure 

Substance Name — Epichlorohydrin 

CASRN — 106-89-8 

Last Revised — 02/01/1994 

Section II provides information on three aspects of the carcinogenic assessment for the 

substance in question; the weight-of-evidence judgment of the likelihood that the substance 

is a human carcinogen, and quantitative estimates of risk from oral exposure and from 

inhalation exposure. The quantitative risk estimates are presented in three ways. The slope 

factor is the result of application of a low-dose extrapolation procedure and is presented as 

the risk per (mg/kg)/day. The unit risk is the quantitative estimate in terms of either risk per 

ug/L drinking water or risk per ug/cu.m air breathed. The third form in which risk is 

presented is a drinking water or air concentration providing cancer risks of 1 in 10,000, 1 in 

100,000 or 1 in 1,000,000. The rationale and methods used to develop the carcinogenicity 

information in IRIS are described in The Risk Assessment Guidelines of 1986 (EPA/600/8-

87/045) and in the IRIS Background Document. IRIS summaries developed since the 

publication of EPA's more recent Proposed Guidelines for Carcinogen Risk Assessment also 

utilize those Guidelines where indicated (Federal Register 61(79):17960-18011, April 23, 

1996). Users are referred to Section I of this IRIS file for information on long-term toxic 

effects other than carcinogenicity. 

_II.A. Evidence for Human Carcinogenicity 

__II.A.1. Weight-of-Evidence Characterization 

Classification — B2; probable human carcinogen 

Basis — Human data are inadequate. Multiple studies in rats and mice administered 

epichlorohydrin by various routes were positive. As epichlorohydrin is a strong alkylating 

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agent, tumors are produced at the site of application. 

__II.A.2. Human Carcinogenicity Data 

Inadequate. A retrospective cohort mortality study has been conducted on 864 workers from 

epichlorohydrin-producing plants in Louisiana and Texas (Enterline, 1981). Deaths were 

compared by cause with those expected for the states of Louisiana and Texas. An interim 

report showed workers to have less than expected overall mortality, but an increase (not 

significant) in both respiratory cancer and leukemia mortality. An update on the exposed 

cohort, however, indicated a reversal of this trend. The study is complicated by the fact that 

of those 10 workers diagnosed with lung cancer, seven were smokers, one was a nonsmoker, 

and the smoking history of two was not known. Furthermore, there is no apparent doseresponse trend, and there is the confounding exposure to the isopropyl alcohol manufacturing 

process concomitant with epichlorohydrin. 

A retrospective cohort mortality study of 533 chemical workers (Shellenberger et al., 1979) 

and an historic prospective study of European workers (Tassignon et al., 1983) failed to 

demonstrate a connection between epichlorohydrin and increased cancer mortality. The first 

study is inadequate for valid carcinogenicity assessment because of low exposure, short 

exposure duration, short study period, and the young age of the cohort. The second study 

suffers from some of the same limitations, as well as that of a small cohort size with at least 

10 years exposure (274 individuals). 

__II.A.3. Animal Carcinogenicity Data 

Sufficient. Epichlorohydrin has produced cancers of various types at the site of application 

when administered by several routes. While ineffective as a complete skin carcinogen, 

epichlorohydrin produced papillomas in mice when used as an initiator followed by phorbol 

myristate acetate promotion (Van Duuren et al., 1974). Local sarcomas developed in mice at 

the site of single subcutaneous injections of epichlorohydrin (Kotin and Falk, 1963). 

Wester et al. (1985) administered 0, 2 or 10 mg/kg/day epichlorohydrin by gavage to groups 

of 50 each male and female Wistar rats. Mortality was high in all female rats during the first 

12 months because of a high-fiber diet. The incidence of forestomach carcinomas was 

significantly increased in the high-dose rats. Konishi et al. (1980) reported similar results in 

male Wistar rats given epichlorohydrin in the drinking water. Drinking water was 

administered to 18 animals each with 0, 375, 750, or 1500 ppm epichlorohydrin. Poor health 

of treated animals necessitated that untreated water be given intermittently during weeks 

60-81. All surviving high-dose rats developed forestomach hyperplasia; forestomach 

papillomas were significantly increased and two squamous cell carcinomas were also noted, 

as well as squamous cell carcinomas of the oral cavity. 

Inhalation exposure of male Sprague-Dawley rats was undertaken by Laskin et al. (1980). 

Animals (140) were exposed to 100 ppm, 6 hours/day for 30 days and observed for their 

lifetime. Nasal cavity tumors, including squamous cell carcinomas, developed in 15/140 rats 

compared to none in either 150 concurrent or in 1920 historical controls. Groups of 100 

animals were exposed to 10 or 30 ppm, 6 hours/day, 5 days/week for their lifetime. By 136 

weeks, 100% mortality was noted. One nasal cavity tumor and two respiratory tract tumors 

were observed among the high-dose rats. 

__II.A.4. Supporting Data for Carcinogenicity

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Epichlorohydrin is a direct-acting mutagen by virtue of its activity as an alkylating agent. 

Positive results have been obtained in mutagenicity tests in several bacterial species, 

Neurospora, Saccharomyces, Drosophilia (including recessive lethal), and cultured 

mammalian cells (reviewed in Sram et al., 1981). Epichlorohydrin causes mitotic 

recombination in yeast and sister-chromatid-exchange and chromosomal aberrations in 

mammalian cells. The latter were observed in lymphocytes obtained from exposed workers 

(Sram et al., 1981; Kucerova et al., 1977; Picciano, 1979). 

_II.B. Quantitative Estimate of Carcinogenic Risk from Oral Exposure 

__II.B.1. Summary of Risk Estimates 

Oral Slope Factor — 9.9E-3 per (mg/kg)/day 

Drinking Water Unit Risk — 2.8E-7 per (ug/L) 

Extrapolation Method — Linearized multistage procedure, extra risk 

Drinking Water Concentrations at Specified Risk Levels: 

__II.B.2. Dose-Response Data (Carcinogenicity, Oral Exposure) 

Tumor Type — papillomas and carcinomas of the forestomach 

Test Animals — rat/Wistar, male 

Route — drinking water 

Reference — Konishi et al., 1980 

__II.B.3. Additional Comments (Carcinogenicity, Oral Exposure) 

Doses are equivalent human doses assuming 70 kg bw, and 2 L water consumption using the 

formula: 

Risk Level Concentration 

E-4 (1 in 10,000) 3E+2 ug/L 

E-5 (1 in 100,000) 3E+1 ug/L 

E-6 (1 in 1,000,000) 3E+0 ug/L 

Administered 

Dose (ppm in d.w.) 

Human Equivalent 

Dose (mg/kg/day) 

Tumor 

Incidence 

0 0 0/10 

375 27.1 0/9 

750 55.7 2/10 

1500 108.6 9/12 

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f water(rat) x water concentration(rat) = 

f water(human) x water concentration(human); 

where: 

f water(rat) = 0.078 (fraction of body weight consumed as water) and 

f water(human) = 0.029. 

Since epichlorohydrin is an alkylating agent, its effect in the forestomach is considered to be 

a local reaction. The unit risk value should not be used if the water concentration exceeds 

3E+4 ug/L, since above this concentration the unit risk may not be appropriate. 

__II.B.4. Discussion of Confidence (Carcinogenicity, Oral Exposure) 

The above study provides the only drinking water data available. Limitations include the 

following: the study was terminated at 81 weeks; epichlorohydrin concentration in the water 

was likely to be overestimated because of its short half-life; dose levels administered were 

toxic to the animals; pathology data obtained on animals dying during the course of the 

study were not considered reliable by the authors; and few animals were used. 

_II.C. Quantitative Estimate of Carcinogenic Risk from Inhalation Exposure 

__II.C.1. Summary of Risk Estimates 

Inhalation Unit Risk — 1.2E-6 per (ug/cu.m) 

Extrapolation Method — Linearized multistage procedure, extra risk 

Air Concentrations at Specified Risk Levels: 

__II.C.2. Dose-Response Data for Carcinogenicity, Inhalation Exposure 

Tumor Type — nasal cavity tumors 

Test Animals — Rat/Sprague-Dawley, male 

Route — inhalation 

Reference — 

Risk Level Concentration 

E-4 (1 in 10,000) 8E+1 ug/cu.m

E-5 (1 in 100,000) 8E+0 ug/cu.m

E-6 (1 in 1,000,000) 8E-1 ug/cu.m

Admin. Dose 

(ppm in air) 

Tumor 

Incidence 

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__II.C.3. Additional Comments (Carcinogenicity, Inhalation Exposure) 

Historical control incidence for these tumors is 0/1920. 

Since epichlorohydrin was administered as a partially soluble vapor, the concentrations in 

ppm administered to the experimental animals are considered equivalent to the same 

concentrations in humans. The unit risk value should not be used if the air concentration 

exceeds 8E+3 ug/cu.m, since above this concentration the unit risk may not be appropriate. 

__II.C.4. Discussion of Confidence (Carcinogenicity, Inhalation Exposure) 

Analysis was based on nonsignificant increases in incidence. The Laskin et al. (1980) study 

did show a strong dose rate effect, as evidenced by the tumor response with the highexposure, short-duration group. A risk estimate including the time-to-tumor, dosing regimen, 

and lung cancer incidence data from 30 days exposure to 100 ppm gives a unit risk of 1.2E-6 

per (ug/cu.m). Data from the epidemiologic study by Enterline (1981) were used to calculate 

the risk estimate of 0.15 per (ppm) or 3.9E-5 per (ug/cu.m) assuming an average exposure 

of 5 ppm and exposure duration of 13.4 years. Risk estimates based on the Laskin (1980) 

and Enterline (1981) studies, thus, varied by at least 1 order of magnitude. 

_II.D. EPA Documentation, Review, and Contacts (Carcinogenicity Assessment) 

__II.D.1. EPA Documentation 

Source Document — U.S. EPA, 1984, 1985 

The values in the 1984 Health Assessment Document for Epichlorohydrin have received both 

Agency and outside review. Those in the 1985 Health and Environmental Effects Profile for 

Epichlorohydrin have been reviewed by Agency groups. 

__II.D.2. EPA Review (Carcinogenicity Assessment) 

Agency Work Group Review — 08/13/1986, 10/29/1986 

Verification Date — 10/29/1986 

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA 

contractor of the more recent toxicology literature pertinent to the cancer assessment for 

Epichlorohydrin conducted in September 2002 identified one or more significant new studies. 

IRIS users may request the references for those studies from the IRIS Hotline at 

hotline.iris@epa.gov or (202)566-1676. 

__II.D.3. EPA Contacts (Carcinogenicity Assessment)

0 0/150 

10 0/100 

30 1/100 

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Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in 

general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet 

address). 

_III. [reserved] 

_IV. [reserved] 

_V. [reserved] 

_VI. Bibliography 

Substance Name — Epichlorohydrin 

CASRN — 106-89-8 

Last Revised — 04/01/1992 

_VI.A. Oral RfD References 

Not available at this time. 

_VI.B. Inhalation RfC References 

Barrow, C.S., W.H. Steinhagen and J.C.F. Chang. 1983. Formaldehyde sensory irritation. 

Chapter 3. In: Formaldehyde Toxicity, J.E. Gibson, Ed. Hemisphere Publishing Company, 

Washington, DC. 

Buckley, L.A., X.Z. Jiang, R.A. James, K.T. Morgan and C.S. Barrow. 1984. Respiratory tract 

lesions induced by sensory irritants at the RD50 concentration. Toxicol. Appl. Pharmacol. 74: 

417-429. 

Chang, J.C.F., E.A. Gross, J.A. Swenberg and C.S. Barrow. 1983. Nasal cavity deposition, 

histopathology, and cell proliferation after single or repeated formaldehyde exposures in 

B6C3F1 mice and F-344 rats. Toxicol. Appl. Pharmacol. 68: 161-176. 

Cooper, E.R.A., A.R. Jones and H. Jackson. 1974. Effects of alpha- chlorohydrin and related 

compounds on the reproductive organs and fertility of the male rat. J. Reprod. Fert. 38: 379-

386. 

Enterline, P., V. Henderson, and G. Marsh. 1990. Mortality of workers potentially exposed to 

epichlorohydrin. Br. J. Ind. Med. 47: 269-276. 

Gage, J.C. 1959. The toxicity of epichlorhydrin vapour. Br. J. Ind. Med. 16: 11-14. 

Hahn, J.D. 1970. Post-testicular antifertility effects of epichlorohydrin and 2,3-

epoxypropanol. Nature. 226: 87. 

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John, J.A., J.F. Quast, F.J. Murray, et al. 1979. The effects of inhaled epichlorohydrin on the 

semen of rabbits and on the fertility of male and female rats. Toxicology Research 

Laboratory, Dow Chemical, Midland, MI. July 1979. NIEHS Contract No. NO1-ES-3-2102. 

(Unpublished) 

John, J.A., J.F. Quast, F.J. Murray, L.G. Calhoun and R.E. Staples. 1983a. Inhalation toxicity 

of epichlorohydrin: Effects on fertility in rats and rabbits. Toxicol. Appl. Pharmacol. 68: 415-

423. 

John, J.A., T.S. Gushow, J.A. Ayres, et al. 1983b. Teratologic evaluation of inhaled 

epichlorohydrin and allyl chloride in rats and rabbits. Fund. Appl. Toxicol. 3: 437-442. 

Kane, L.E., C.S. Barrow and Y. Alarie. 1979. A short-term test to predict acceptable levels of 

exposure to airborne sensory irritants. Am. Ind. Hyg. Assoc. J. 40: 207-229. 

Kluwe, W.M., B.N. Gupta and J.C. Lamb. 1983. The comparative effects of 1,2- dibromo-3-

chloropropane (DBCP) and its metabolites, 3-chloro-1,2-propaneoxide (epichlorohydrin), 3-

chloro-1,2-propanediol (alphachlorohydrin), and oxalic acid, on the urogenital system of male 

rats. Toxicol. Appl. Pharmacol. 70: 67-86. 

Laskin, S., A.R. Sellakumar, M. Kuschner, et al. 1980. Inhalation carcinogenicity of 

epichlorohydrin in noninbred Sprague-Dawley rats. J. Natl. Cancer Inst. 65(4): 751-757. 

Milby, T.H. and D. Whorton. 1980. Epidemiological assessment of occupationally related, 

chemically induced sperm count suppression. J. Occup. Med. 22(2): 77-82. 

Milby, T.H., M.D. Whorton, H.A. Stubbs, et al. 1981. Testicular function among 

epichlorohydrin workers. Br. J. Ind. Med. 38: 372-377. 

Pilny, M.K., T.S. Lederer, J.S. Murray, et al. 1979. Epichlorohydrin - subchronic studies. IV. 

The effects of maternally inhaled epichlorohydrin on rat and rabbit embryonal and fetal 

development. Toxicology Research Laboratory, Health and Environmental Sciences, Dow 

Chemical U.S.A., Midland, MI. 8D submission. Microfiche No. 206200. (Unpublished). 

Quast, J.F., J.W. Henck, B.J. Postma, D.J. Schuetz and M.J. Mckenna. 1979a. Epichlorohydrin 

- subchronic studies. I. A 90-day inhalation study in laboratory rodents (Fischer 344 rats, 

Sprague-Dawley rat and B6C3F1 mice). 8D submission. Microfiche No. 206200. 

(Unpublished). 

Quast, J., T. Lederer, B. Postma, et al. 1979b. A 12-day inhalation study in laboratory 

rodents (Fischer 344 rats, Sprague-Dawley rats and B6C3F1 mice) prepared by Dow 

Chemical. Doc. No. 878210083. Fiche No. OTS0206200. January 12. (Unpublished). 

Slott, V.L., J.D. Suarez, J.E. Simmons and S.D. Perreault. 1990. Acute inhalation exposure to 

epichlorohydrin transiently decreases rat sperm velocity. Fund. Appl. Toxicol. 15: 597-606. 

Smith, F., P. Langvardt, and J. Young. 1979. Pharmacokinetics of epichlorohydrin (EPI) 

administered to rats by gavage or inhalation. Doc. No. 878210080. Fiche. No. OTS0206200. 

Prepared by Dow Chemical. January 12. (Unpublished). 

Toth, G.P., H. Zenick and M.K. Smith. 1989. Effects of epichlorohydrin on male and female 

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reproduction in Long-Evans rats. Fund. Appl. Toxicol. 13: 16-25. 

Toth, G.P., J.A. Stober, H. Zenick, et al. 1991. Correlation of sperm motion parameters with 

fertility in rats treated subchronically with epichlorohydrin. J. Androl. 12: 54-61. 

Tsai, S., S. Cowles, D. Tackett, M. Barclay, and C. Ross. 1990. Morbidity prevalence study of 

workers with potential exposure to epichlorohydrin. Br. J. Ind. Med. 47(6): 392-399. 

Union Carbide. 1983. Epichlorohydrin repeated inhalation, preliminary metabolic studies, 

revision of acute toxicity data, and human sensory response. U.S. EPA/OPTS Public Files. 8D 

submission. Microfiche No. 0206066. OTS 84003A. (Unpublished). 

U.S. EPA. 1984. Health Assessment Document for Epichlorohydrin. Prepared by the Office of 

Health and Environmental Assessment, Environmental Criteria and Assessment Office, 

Research Triangle Park, NC for the Office of Air Quality Planning and Standards, Research 

Triangle Park, NC. EPA-600/8-83-032F. 

U.S. EPA. 1985a. Health and Environmental Effects Profile for Epichlorohydrin. Prepared by 

the Office of Health and Environmental Assessment, Environmental Criteria and Assessment 

Office, Cincinnati, OH for the Office of Solid Waste, Washington, DC. (Final Draft). 

U.S. EPA. 1985b. Drinking Water Criteria Document for Epichlorohydrin. Prepared by the 

Office of Health and Environmental Assessment, Environmental Criteria and Assessment 

Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. External Review 

Draft. Final Draft (on Public Comment). NTIS PB 86-118023. EPA-600/X-84-200-2. 

Venable, J.R., C.D. McClimans, R.E. Flake and D.B. Dimick. 1980. A fertility study of male 

employees engaged in the manufacture of glycerine. J. Occup. Med. 22(2): 87-91. 

_VI.C. Carcinogenicity Assessment References 

Enterline, P.E. 1981. Further update of mortality among workers exposed to epichlorohydrin. 

Report to Shell Oil Co., Jan. 13, 1981. Submitted to Environmental Protection Agency, Office 

of Toxic Substances. Docket No. 8EHQ- 0878-0230 Supplement. 

Konishi, T., A. Kawabata, A. Denda, et al. 1980. Forestomach tumors induced by orally 

administered epichlorohydrin in male Wistar rats. Gann. 71: 922-923. 

Kotin, P. and H.L. Falk. 1963. Organic peroxides, hydrogen peroxide, epoxides, and 

neoplasia. Radiat. Res. Suppl. 3: 193-211 

Kucerova, M., V.S. Zhurkov, Z. Polwkova and J.E. Ivanova. 1977. Mutagenic effect of 

epichlorohydrin. II. Analysis of chromosomal aberrations in lymphocytes of persons 

occupationally exposed to epichlorohydrin. Mutat. Res. 48: 355-360. 

Laskin, S., A.R. Sellakumar, M. Kuschner, et al. 1980. Inhalation carcinogenicity of 

epichlorohydrin in noninbred Sprague-Dawley rats. J. Natl. Cancer Inst. 65(4): 751-757. 

Picciano, D. 1979. Cytogenic investigation of occupational exposure to epichlorohydrin. 

Mutat. Res. 66: 169-173. 

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Shellenberger, R.J., C.D. McClimans, M.G. Ott, R.E. Flake and R.L. Daniel. 1979. An 

evaluation of the mortality experience of employees with potential for exposure to 

epichlorohyrdrin. Unpublished study submitted to the U.S. Department of Labor, OSHA 

Docket No. H-100. 

Sram, R.J., L. Tomatis, J. Clemmessen and B.A. Bridges. 1981. An evaluation of the genetic 

toxicity of epichlorohydrin. Mutat. Res. 87: 299-319. 

Tassignon, J.P., G.D. Bos, A.A. Craigen, et al. 1983. Mortality in a European cohort 

occupationally exposed to epichlorohydrin (ECH). Unpublished. 

U.S. EPA. 1984. Health Assessment Document for Epichlorohydrin. Prepared by the 

Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Air Quality 

Planning and Standards, Washington, DC. 

U.S. EPA. 1985. Health and Environmental Effects Profile for Epichlorohydrin. Prepared by the 

Office of Health and Environmental Assessment, Environmental Criteria and Assessment 

Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response, Washington, 

DC. 

Van Duuren, B.L., B.M. Goldschmidt, C. Katz, I. Seidman and J.S. Paul. 1974. Carcinogenic 

activity of alkylating agents. J. Natl. Cancer Inst. 53: 695-700. 

Wester, P.W., C.A. Van Der Heijden, A. Bisschop and G.J. Van Esch. 1985. Carcinogenicity 

study with epichlorohydrin (CEP) by gavage in rats. Toxicology. 36: 325-339 

_VII. Revision History 

Substance Name — Epichlorohydrin 

CASRN — 106-89-8 

Date Section Description

09/30/1987 V. Supplementary Data section added

03/01/1988 I.A.1. Dose conversion factor corrected

03/01/1988 I.A.2. Text clarified

03/01/1988 II.B.1. Number rounded off

03/01/1988 II.B.3. Text revised

03/01/1988 II.B.4. Confidence statement revised

03/01/1988 II.C. Slope factor changed

03/01/1988 II.C.1. Number rounded off

03/01/1988 II.C.3. Text revised

03/01/1988 II.C.4. Confidence statement revised

03/01/1988 III.A. Health Advisory added

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_VIII. Synonyms 

Substance Name — Epichlorohydrin 

CASRN — 106-89-8 

Last Revised — 01/31/1987 

106-89-8 

1-chlor-2,3-epoxypropane 

06/30/1988 II.D.1. Documentation corrected

06/01/1989 I.A.6. Work group review date added

10/01/1989 I.B. Inhalation RfC now under review

02/01/1990 II.A.2. Shellenberger et al., 1979 spelling corrected

02/01/1990 VI. Bibliography on-line

06/01/1990 IV.A.1. Area code for EPA contact corrected

08/01/1990 III.A.10 Primary contact changed

01/01/1991 II. Text edited

01/01/1991 II.C.1. Inhalation slope factor removed (global change)

09/01/1991 I.A. Oral RfD summary noted as pending change

01/01/1992 I.A.7. Secondary contact changed

01/01/1992 IV. Regulatory actions updated

04/01/1992 I.A. Oral RfD summary withdrawn pending further review

04/01/1992 I.B. Inhalation RfC summary on-line

04/01/1992 IV.A.1. CAA regulatory action withdrawn

04/01/1992 VI.A. Oral RfD references withdrawn

04/01/1992 VI.B. Inhalation RfC references added

06/01/1992 III.A.5. DWEL withdrawn

02/01/1994 II.D.3. Secondary contact's phone number changed

08/01/1995 I.A., 

I.A.6., 

VI.A.

EPA's RfD/RfC and CRAVE workgroups were discontinued in May, 

1995. Chemical substance reviews that were not completed by 

September 1995 were taken out of IRIS review. The IRIS Pilot 

Program replaced the workgroup functions beginning in 

September, 1995.

04/01/1997 III., IV., 

V.

Drinking Water Health Advisories, EPA Regulatory Actions, and 

Supplementary Data were removed from IRIS on or before April 

1997. IRIS users were directed to the appropriate EPA Program 

Offices for this information.

12/03/2002 I.A., 

I.B.6., 

II.D.2.

Screening-Level Literature Review Findings message has been 

added.

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chloromethyloxirane 

2-chloropropylene oxide 

y-chloropropyleneoxide 

epichlorhydrin 

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