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0050 Epichlorohydrin; CASRN 106-89-8
Health assessment information on a chemical substance is in cluded in IRIS only after a comprehensive review of chronic toxicity data by U.S. EPA health sci entists 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 re view 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 Assess ments 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Chronic Oral Exposure (RfD) Substance Name — Epichlorohydrin CASRN — 106-89-8 The Oral RfD for this substance has been withdrawn pending further review by the RfD/RfC Work Group.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 Search IRIS by Keyword

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Reference Dose for Chronic Oral Exposure ( RfD )

Cate g or y ( section ) Status Last Revised Oral RfD Assessment (I.A.) withdrawn 04/01/1992 Inhalation RfC Assessmen t (I.B.) on-line 04/01/1992 Carcinogenicity Assessmen t (II.) on-line 02/01/1994 

## Integrated Risk Information System htt p ://www.e p a. g ov/iris/subst/0050.htm Last u p dated on Monda y, March 07 , 2011 

### Iris Camacho, 6308MM Pa g e 1 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmcontractor of the more recent toxicology literature pertinent to the RfD for Epichlorohydrin conducted in September 2002 identified one or mo re significant new studies. IRIS users may request the references for th ose studies from the IRIS Ho tline at hotline.iris@epa.gov or (202)566-1676.

EPA Contacts: Please contact the IRIS Hotline for all questi ons 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 exis t for certain toxic effe cts such as cellular necrosis. The inhalation RfC considers toxic effe cts for both the respirat ory system (portal-ofentry) and for effects peripheral to the respiratory system (ext rarespiratory 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 in halation 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 (E PA/600/8-90/066F October 1994). RfCs can also be derived for the noncarcinoge nic health effects of substa nces that are carcinogens. Therefore, it is essential to refer to ot her 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 degree s 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 Ex p osures* 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 

### Iris Camacho, 6308MM Pa g e 2 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmcu.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 RG DR = 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 St udy in Laboratory Rodents. 8D Submission. Microfiche No. 206200. In a 3-month study, groups of B6C3F1 mice, Fischer 344 rats, and Sp rague- 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 warm ed vaporization flask then passed through the chamber airflow with compressed air. The dynamic airflow conditions were maintained at 70- 75 degrees F and relative humidi ty at 40-60%. Animals were ob served for clinical signs of toxicity and measured bi weekly 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 eval uated except that hist ological observations were made on only five animals per concentr ation in the control an d 50-ppm animals at the interim sacrifice. At the 3-month terminal sacrif ice, animals in all groups were evaluated for histopathological effect s 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 (m ales, 9/10, 10/10; fema les, 8/10, 10/10, resp ectively) and SpragueDawley rats (males, 9/10, 10/10; females, 10/10, 10/10, resp ectively). This effect was observed in all exposed rats in the 50-ppm gr oup 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 infl ammatory exudate were al so 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 pneumo nitis was observed in most of the control and exposed rats of both strains, making conclusion s about possible effects in the pulmonary region impossible. Inflammation of the nasal turbinates (described as focal subepithelial mononuclear cell infiltrate) was obse rved in most rats of both strains in the control and 5 ppm groups but no t in the 25- and 50- ppm groups. This le sion indicates an underlying inflammatory reaction in these ti ssues which is not expo sure-related. However, the location of this lesion make s it distinct from the epithelia l 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-Da wley 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 appear ance) were also exhibited in female rats exposed to 50 ppm. No other tr eatment-related effects were observed. The NOAEL of 5 ppm epichlorohydrin was determined for na sal 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 volu me; RGDR = 0.107 - 0.206 based on respiratory effects in the extrathoracic region]. A NOAEL for kidney effe cts is identified at 25 ppm [NOAEL(HEC) = 17 mg/cu.m]. The respiratory effects in rats are us ed for derivation of the RfC because of the greater severity of the lesion in rats, the involvement of respiratory and olfactory epithelium, 

### Iris Camacho, 6308MM Pa g e 3 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmand the lower calculated NOAEL(HEC).

Results in mice after 3 monthsshowed 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 female s in the 50-ppm group co mpared with 0/10 in the controls at the 30-day sacrifice. Suppura tive inflammatory exud ate or mucus in the lumen of the nasal turbinateswere 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 ot her clearly exposure- re lated effects observed. However, 2, 1, 0, and 0 males and 9, 9, 0, and 0 females in the cont rol, 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 co ncentrations. Inflammatory reactions in the tracheobronchiolar and pulmonary region, whic h may have been treatment related, were observed in a few animals in the high- concentration groups. All other microscopic findings were interpreted to be spontane ous. There was no indication th at the investigators tested for viral infection. A NOAEL of 5 ppm was establishe d for changes in the nasa l turbinates of mice (HEC = 0.41 mg/cu.m, based on respiratory tr act effects in the extr athoracic region in females). The HEC for nasal effe cts 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 decr ease their minute volume by up to 75% as compared with a maximal 45% reduction in ratswhen exposed to formaldehyde (Barrow et al., 1983; Chang et al., 1983). This study suppo rts the finding of nasal effects at 25 and 50 ppm in rats. __I.B.3. Uncertainty and Modi fying Factors (Inhalation RfC) UF — An uncertainty factor of 300 reflects a factor of 10 to account for sensitive human subpopulations and 3 to account fo r interspecies extrapolation. An additional factor of 10 was applied to account for extrapol ation from a subchronic study and for data deficiencies, including the lack of a 2-gene ration reproduction study.

MF — None __I.B.4. Additional Studies/ Comments (Inhalation RfC) Quast et al. (1979b) conducted a short-term st udy in Fischer 344 rats, Sprague-Dawley rats, and B6C3F1 mice (5/species/sex/ concentratio n). There were nine exposures of 0 or 100 ppm (378 mg/cu.m) to epichlorohydrin 7 hour s/day, 5 days/week fo r 12 days. Significant decreased body weight gain, thymic atrophy, in creased relative kidney weights (rats only), and leukocytosis were reported in the 100- ppm exposed animals for both rat strains. Degeneration, discoloration, in flammation, and hype rplasia of the nasal turbinates were consistently observed to some degree in all ex posed animals. These e ffects were located in the respiratory epithelium of mice and in the respiratory and olfactory epithelium of rats. Changes in the kidney (e.g., discoloration, tubu lar 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 mi ce. Mononuclear cell infiltrate in the tracheobronchial and pulmonary region was observed in most rats (control and exposed) and in slightly more 

### Iris Camacho, 6308MM Pa g e 4 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmexposed 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-adju sted to 4, 6.3, 13, 17, and 34 mg/cu.m). Groups of two hybrid Basanji-Cocker dogs and two Rh esus 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 ki dneys and liver were weighed and the tissues examined for hi stopathological changes. Exposure-related deaths occurred in rats exposed at 68 ppm or greater. These an imals exhibited lung irritation, kidney injury, and weight gain depres sion. In the rat, a NOAEL of 43 ppm (HEC = 34 mg/cu.m) was determined for these extrar espiratory effects. In the 21-ppm exposed monkeys and dogs, lung effects (e.g., hemoside rin deposits, bronchial irritation, and focal proliferation of alveolar sept a), 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 thes e findings. The study wa s also limited because the nasal turbinates were not examined an d too few dogs and mo nkeys were tested. In a chronic bioassay, groups of 100 male Spra gue-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 (136weeks) (Laskin et al., 1980). The control animals were sham exposed or un treated. 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 dege nerative 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 report ed that, qualitatively, the le sions in exposed animals were similar to those observed in the controls. The se verity 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 change s (not further specifie d) 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 tr ee and upper respiratory region we re 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 gr oup 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 hour s/day, 5 days/week for a total of 11-19 exposures. No controls are reported. No effect s were noted at 9 and 17 ppm. Exposure to 27 ppm resulted in respiratory irritation, but cr iteria for this judgme nt were not discussed. Lethargy, weight loss, respiratory distress and nasal discharge were observed at 56 ppm, but no histological effects were no ted in the lungs. Ex posure to 120 ppm resu lted 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. 

### Iris Camacho, 6308MM Pa g e 5 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmAcute exposures (6 hours) to 283-445 ppm epic hlorohydrin resulted in severe pulmonary edema, hemorrhage, and incr eased lung-to-body weight ratio (Laskin et al., 1980). Kane et al. (1979) exposed male Swiss-Webs ter mice to a range of epichlorohydrin concentrations for 15 minutes and measured the decrease in respirator y 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 epichl orohydrin 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 respir atory 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 mo ribund condition at th e end of the exposure. Histopathology of the re spiratory tract showed ulceration an d necrosis in the respiratory and olfactory epithelium of the nose as well as trac heal epithelial exfoliat ion and hyperplasia and slight bronchiolar exfoliation. Thirty Sprague-Dawley rats/sex/concentration and 10 male New Zealand white rabbits/concentration were ex posed 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 dura tion 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 post exposure period, 10 rats/sex/concentration and the remaining rabbits were killed and examined for histopathologic changes. Histop athology was performed on an extensive list of tissues including kidney, liver, lung, trachea, and four sections of the nose. Twenty-five exposed male rats we re 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 hour s per day for 7 days. The 25 exposed female rats were mated with unexposed males after the 10-week exposure. Th ere was a significant reduction in the fertility of the 50-ppm expose d 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 sign ificant. The average num ber of implants in unexposed females that mated with exposed ma les was significantly (p <0.005) lower in the 25-and 50-ppm males during the ex posure 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 peri od showed no effect on estrous pattern, percent pregnant, gestation length, litter size, orpup survival at two days. Ther efore, a NOAEL of 5 ppm (HEC = 3.4 mg/cu.m) was calculated for reproductive toxicity in male rats. The high-concentration group show ed 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., infla mmation, 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 peri od. 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 ef fects described in the principal study. Since these findings were not exhibite d in animals at the final sacrif ice (10 weeks post exposure), 

### Iris Camacho, 6308MM Pa g e 6 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmthe changes in the nasal turbinateswere considered reversible. In the rabbits, 10 animals per concentration we re mated during week 10 of exposure. No reproductive effects were note d in rabbits exposed to epic hlorohydrin including percent fertile; number of implantati ons; and based on weekly exam ination, no effect on sperm viability, motility, or number. In the 25- an d 50-ppm groups, exposed rabbits had bilateral suppurative rhinitis or sinusitis and pneumonia compared with controls. Th e 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 in flammation 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 epichlorohydri n 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 revers ible 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 ra ts 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 an imals and no effects were seen on reproduction in exposed female s. Male fertility was examined in high-dose males only and they were found to be infert ile. No effect was observed on copulatory behavior, sperm counts, or sperm morphology. Significantly reduced linear velocity and curvilinear velocity was observed in expose d animals at 12.5 mg/kg/day and higher, and reduced linearity of motion was observed at50 mg/kg/day. The percent motile sperm was reported to be unaffected in th is study, but a later reanalysis (Toth et al., 1991) reported this parameter to be significantly a ffected at 25 and 50 mg/kg/day. In a further examination of reproductive effects by the inha lation route, Slott et al. (1990) exposed rats to 100 ppm for a single 4-hour exposure. No effe ct was seen on percent motile sperm or sperm counts at 1-14 days post exposure. Significant de creases were reported in curvili near and linear velocity at 1 day post exposure but not at 2-14 days post exposure. These studies show a specific effe ct 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 co nsidered to reflect sperm energy utilization. In a study designed to eval uate the correlation between sperm motion parameters and fertility measures, Toth et al. (1991) dosed male rats or ally with 6.25, 12.5, and 25 mg/kg/day epichlorohydrin for 23 days. Expose d 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 exposu re, 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 sh own no evidence of reduced sperm count in the exposed groups. De tailed measurement of sperm motion has not been applied to an occupati onally exposed population. These reproductive studies indicate that the reproductive toxicity of epichlorohydrin is 

### Iris Camacho, 6308MM Pa g e 7 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmprobably mediated by an effect on mature sper m, and that fertility ef fects are observed at lower epichlorohydrin doses than effects on sperm morphology, production, or testicular histology. Histopathology of the reproductive organs has b een observed at much higher doses by oral and injection rout es than doses shown to affect fertility (Cooper et al., 1974; Kluwe et al., 1983). The effects show a rapid on set and a rapid and complete reversal after exposure ends. In a developmental toxici ty 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 rabbi ts, 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 reco rded and fetuses were examined fo r external, soft tissue (one-third fetuses), and skeletal abnormal ities. In the high-concentration rats, maternal weight was significantly decreased on days 6, 8, 10, 12, and 16 of gestation. Howe ver, maternal weights were reported to be sign ificantly 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 ex cept 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, ther e were no significant effects on fetal body weight, number of corpora lutea, live fetuses, implantations, resorption s, 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 result ed in a 5-fold greater amount of radioactivity per tissue mass in the nasal tu rbinates than the lungs. In humans, epichlorohydrin is known to cause respiratory irritation. However, occupational studies other than those fo cused on reproductive effe cts discussed above have only evaluated mortality in work ers (Enterline et al., 19 90; 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 examin ations of numerous tissues including the respiratory tract. However, it was given a medi um confidence because of the inflammation in the respiratory tract of cont rol and exposed animals. The database is given a medium confidence because chro nic studies which adequately addr ess 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 infla mmation 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 pres ented in any existing U.S. EPA document. 

### Iris Camacho, 6308MM Pa g e 8 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmOther 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 mo re significant new studies. IRIS users may request the references for th ose studies from the IRIS Ho tline at hotline.iris@epa.gov or (202)566-1676. __I.B.7. EPA Contacts (Inhalation RfC) Please contact the IRIS Hotline for all questi ons 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 Assessme nt for Lifetime Exposure Substance Name — Epichlorohydrin CASRN — 106-89-8 Last Revised — 02/01/1994 Section II provides information on three aspe cts of the carcinogenic assessment for the substance in question; the weig ht-of-evidence judgment of the likelihood that the substance is a human carcinogen, and quantitative estima tes of risk from oral exposure and from inhalation exposure. The quantitative risk es timates are presented in three ways. The slope factor is the result of application of a low-do se extrapolation procedure and is presented as the risk per (mg/kg)/day. The unit risk is the qu antitative 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 concentrat ion providing cancer risks of 1 in 10,000, 1 in 100,000 or 1 in 1,000,000. The rati onale and methods used to develop the carcinogenicity information in IRIS are described in The Ri sk Assessment Guidelines of 1986 (EPA/600/8- 87/045) and in the IRIS Background Docume nt. IRIS summaries developed since the publication of EPA's more recent Proposed Guidelines for Carcinogen Risk Assessment also utilize those Guidelines wher e indicated (Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to Section I of this IR IS file for informatio n on long-term toxic effects other than carcinogenicity. _II.A. Evidence for Human Carcinogenicity __II.A.1. Weight-of-Evid ence 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 

### Iris Camacho, 6308MM Pa g e 9 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmagent, tumors are produced atthe site of application. __II.A.2. Human Carcinogenicity Data Inadequate. A retrospective coho rt mortality study has been conducted on 864 workers from epichlorohydrin-producing plan ts in Louisiana and Texas (E nterline, 1981). Deaths were compared by cause with those expected for th e 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 le ukemia 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 th e confounding exposure to the isopropyl alcohol manufacturing process concomitant with epichlorohydrin. A retrospective cohort mortalit y study of 533 chemical workers (Shellenberger et al., 1979) and an historic prospe ctive study of European workers (T assignon et al., 1983) failed to demonstrate a connection between epichlorohydri n and increased cancer mortality. The first study is inadequate for valid carcinogenicity assessment because of low exposure, short exposure duration, short study period, and th e young age of the cohort. The second study suffers from some of the same li mitations, 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 pr oduced cancers of various type s 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 sa rcomas developed in mice at the site of single subcutaneo us injections of epichloroh ydrin (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 hi gh-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 untreate d water be given interm ittently during weeks 60-81. All surviving high-dose rats develo ped forestomach hyperplasia; forestomach papillomas were significantly in creased and two squamous cell carcinomas were also noted, as well as squamous cell carc inomas of the oral cavity. Inhalation exposure of male Sprague-Dawley rats was undert aken 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 squamo us 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 hour s/day, 5 days/week for their lifetime. By 136 weeks, 100% mortality was noted. One nasal ca vity tumor and two respiratory tract tumors were observed among the high-dose rats.

__ II.A.4. Su pp ortin g Data for Carcino g enicit y 

### Iris Camacho, 6308MM Pa g e 10 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmEpichlorohydrin is a direct-acting mutagen by virtue of its activity as an alkylating agent. Positive results have been obtained in muta genicity tests in seve ral bacterial species, Neurospora, Saccharomyces, Drosophilia (in cluding 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 Carcin ogenic 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 — Li nearized multistage procedure, extra risk Drinking Water Concentrations at Specified Risk Levels:

__II.B.2. Dose-Response Data (C arcinogenicity, Oral Exposure) Tumor Type — papillomas and ca rcinomas of the forestomach Test Animals — ra t/Wistar, male Route — drinking water Reference — Konishi et al., 1980

__II.B.3. Additional Comments (C arcinogenicity, 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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8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmf 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 no t 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 th e authors; and few animals were used.

_II.C. Quantitative Estimate of Carcinog enic Risk from Inhalation Exposure __II.C.1. Summary of Risk Estimates Inhalation Unit Risk — 1.2E-6 per (ug/cu.m) Extrapolation Method — Li nearized multistage procedure, extra risk Air Concentrations at Specified Risk Levels:

__II.C.2. Dose-Response Data for Ca rcinogenicity, 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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8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htm__II.C.3. Additional Comments (Car cinogenicity, Inhalation Exposure)
Historical control incidence fo r these tumors is 0/1920. Since epichlorohydrin was administered as a partially soluble vapor, the concentrations in ppm administered to the expe rimental animals are consider ed 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 abov e this concentration the unit risk may not be appropriate. __II.C.4. Discussion of Confidence (C arcinogenicity, Inhalation Exposure) Analysis was based on no nsignificant increases in incidenc e. The Laskin etal. (1980) study did show a strong dose rate effect, as evidenced by the tu mor 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 ex posure to 100 ppm gives a unit risk of 1.2E-6 per (ug/cu.m). Data from the ep idemiologic 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 Docume nt for Epichlorohydrin have received both Agency and outside review. Thos e in the 1985 Health and Environmental Effects Profile for Epichlorohydrin have been re viewed 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 pertinen t to the cancer assessment for Epichlorohydrin conducted in Se ptember 2002 identified one or mo re 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 ( Carcino g enicit y Assessment ) 0 0/150 10 0/100 30 1/100 

### Iris Camacho, 6308MM Pa g e 13 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmPlease contact the IRIS Hotline for all questi ons 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. Stei nhagen and J.C.F. Chang. 1983. Fo rmaldehyde 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 irri tants 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 sing le 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 al pha- chlorohydrin and related compounds on the reproductive organs and fertil ity 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 epichlorhydr in vapour. Br. J. Ind. Med. 16: 11-14. Hahn, J.D. 1970. Post-testicular antifertili ty effects of epic hlorohydrin and 2,3- epoxypropanol. Nature. 226: 87. 

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8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmJohn, 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 ma le 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. Mu rray, L.G. Calhoun and R.E. Stap les. 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 an d rabbits. Fund. Appl. Toxicol. 3: 437-442. Kane, L.E., C.S. Barrow and Y. Alarie. 1979. A shor t-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 comparativ e effects of 1,2- dibromo-3- chloropropane (DBCP) and its me tabolites, 3-chloro-1,2-propa neoxide (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 Sp rague-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. Occu p. 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 Rese arch Laboratory, Health and Environmental Sciences, Dow Chemical U.S.A., Midland, MI. 8D submis sion. 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. Mi crofiche No. 206200. (Unpublished). Quast, J., T. Lederer, B. Po stma, et al. 1979b. A 12-day inha lation study in laboratory rodents (Fischer 344 rats, Sprague-Dawley rats and B6C3F1 mice) prepared by Dow Chemical. Doc. No. 878210083. Fiche No. OT S0206200. 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, an d J. Young. 1979. Pharmacokinet ics of epichlorohydrin (EPI) administered to rats by gavage or inha lation. Doc. No. 878210080. Fiche. No. OTS0206200. Prepared by Dow Chemical. January 12. (Unpublished). Toth, G.P., H. Zenick and M.K. Smith. 1989. Ef fects of epichlorohydri n on male and female 

### Iris Camacho, 6308MM Pa g e 15 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmreproduction in Long-Evans rats. Fund. Appl. Toxicol. 13: 16-25. Toth, G.P., J.A. Stober, H. Zeni ck, 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 sensor y response. U.S. EPA/OP TS Public Files. 8D submission. Microfiche No. 0 206066. OTS 84003A. (Unpublished).

U.S. EPA. 1984. Health Assessment Document for Epichlorohydrin. Prepar ed by the Office of Health and Environmental A ssessment, Environmental Crit eria and Assessment Office, Research Triangle Park, NC for the Office of Air Quality Planning an d Standards, Research Triangle Park, NC. EPA-600/8-83-032F.
U.S. EPA. 1985a. Health and Environmental Effe cts Profile for Epichlorohydrin. Prepared by the Office of Health and Environmental Asse ssment, Environmental Cr iteria and Assessment Office, Cincinnati, OH for the Office of So lid Waste, Washington, DC. (Final Draft). U.S. EPA. 1985b. Drinking Water Criteria Docu ment for Epichlorohydrin. Prepared by the Office of Health and Enviro nmental Assessment, Environment al Criteria and Assessment Office, Cincinnati, OH for the Office of Drin king Water, Washington , DC. External Review Draft. Final Draft (on Pub lic 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 fertil ity study of male employees engaged in the manufacture of gl ycerine. J. Occup. Med. 22(2): 87-91.

_VI.C. Carcinogenicity Assessment References Enterline, P.E. 1981. Further up date of mortality among worker s exposed to epichlorohydrin. Report to Shell Oil Co., Jan. 13, 1981. Submitted to Environment al 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 epichloroh ydrin in male Wistar rats. Gann. 71: 922-923. Kotin, P. and H.L. Falk. 1963. Organic peroxides, hydrog en peroxide, epoxides, and neoplasia. Radiat. Re s. Suppl. 3: 193-211 Kucerova, M., V.S. Zhurkov, Z. Polwkova an d J.E. Ivanova. 1977. Mutagenic effect of epichlorohydrin. II. Analysis of chromoso mal aberrations in lymphocytes of persons occupationally exposed to epichloroh ydrin. Mutat. Res. 48: 355-360. Laskin, S., A.R. Sellakumar, M. Kuschner, et al. 1980. Inhalation carcinogenicity of epichlorohydrin in noninbred Sp rague-Dawley rats. J. Natl. Cancer Inst. 65(4): 751-757. Picciano, D. 1979. Cytogenic inve stigation of occupational ex posure to epichlorohydrin. Mutat. Res. 66: 169-173. 

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8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmShellenberger, R. J., C.D. McClimans, M. G. Ott, R.E. Flake an d 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. Cl emmessen 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. Mort ality in a European cohort occupationally exposed to epichl orohydrin (ECH). Unpublished.

U.S. EPA. 1984. Health Assessment Document for Epichlorohydrin. Prepared by the Environmental Criteria and Asse ssment Office, Cincinnati, OH for the Office of Air Quality Planning and Standard s, Washington, DC. U.S. EPA. 1985. Health and Environmental Effects Profile for Epichlorohydrin. Prepared by the Office of Health and Enviro nmental Assessment, Environment al Criteria and Assessment Office, Cincinnati, OH for the Office of So lid Waste and Emergency Response, Washington, DC. Van Duuren, B.L., B.M. Goldschmi dt, 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 Heij den, A. Bisschop and G.J. Van Esch. 1985. Carcinogenicity study with epichlorohydri n (CEP) by gavage in ra ts. Toxicology. 36: 325-339



### _VII. Revision History Substance Name — Epichlorohydrin CASRN — 106-89-8

Date Section Descri p tion 09/30/1987 V. Supplementary Data section added 03/01/1988 I.A.1. Dose conver sion 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. Confidenc e 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. Confidenc e 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-e p ox yp ro p ane 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 etal., 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 fa ctor 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 wi thdrawn 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 re ferences 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 cont act's phone number changed 08/01/1995 I.A., I.A.6., VI.A. EPA's RfD/RfC and CRAVE workgrou ps were discontinued in May, 1995. Chemical substance reviews that were not completed by September 1995 were taken out of IRIS review. Th e IRIS Pilot Program replaced the workgr oup 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. 

### Iris Camacho, 6308MM Pa g e 18 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmchloromethyloxirane 2-chloropropylene oxide y-chloropropyleneoxide epichlorhydrin

IRIS Home Chronic HealthHazards for NonCarcinogenic Effects Reference Dose for Chronic Oral Exposure (RfD)

Oral RfD Summary Principal and Supporting Studies Uncertainty and Modifying Factors Additional Studies/Comments Confidence in the Oral RfD EPA Documentation and Review

Reference Concentration for Chronic Inhalation

Exposure (RfC)

Inhalation RfC Summary Principal and Supporting Studies Uncertainty and Modifying Factors Additional Studies/Comments Confidence in the Inhalation RfC EPA Documentation and Review Carcinogenicity Assessment for Lifetime Exposure Evidence for Human Carcinogenicity

Weight-ofEvidence Characterization Human Carcinogenicity Data Animal Carcinogenicity Data Supporting Data for 

### Iris Camacho, 6308MM Pa g e 19 of 20 Epichlorohy drin (CASRN 106-89-8) | IRIS | US EPA

8/9/2011 http ://www.ep a. g ov/iris/subst/0050.htmCarcinogenicity Quantitative Estimate of Carcinogenic Risk from Oral Exposure Summary of Risk Estimates Dose-Response Data Additional Comments Discussion of Confidence Quantitative Estimate of Carcinogenic Risk

from Inhalation Exposure Summary of Risk Estimates Dose-Response Data Additional Comments Discussion of Confidence EPA Documentation, Review and, Contacts Bibliography Revision History Synonyms 

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