Acute toxicity

Lowest oral LD₅₀ (rabbit) = 55 mg/kg-bw (Rowe et al., 1952)

Lowest inhalation LC₅₀ (rat) = 3080 mg/m³ (Rowe et al., 1952)

[Additional studies: Koptagel and Bulut (1998)]

Short-term repeated-dose toxicity

Lowest oral (gavage) LOEL (mice) = 125 mg/kg-bw per day, based on increased cholesterol levels and increased in vitro phagocytosis of cultured cells from dosed animals (Ratajczak et al., 1994)

Subchronic toxicity

Lowest oral (gavage) LOEL (mice) = 125 mg/kg-bw per day, based on alterations in in vivo serum and hematology parameters and in vitro lymphocyte response (Ratajczak et al., 1995)

Lowest inhalation LOEC (rats) = 77 mg/m³, based on epithelial hyperplasia of the nasal turbinates (Nitschke et al., 1981)

[Additional studies: Reznik et al. (1980)]

Chronic toxicity/ carcinogenicity

Oral (gavage) carcinogenicity bioassay in rats: Males were exposed to a time-weighted average of 0, 38 or 41 mg/kg-bw per day (5 days per week for up to 49 weeks). Females were exposed to 0, 37 or 39 mg/kg-bw per day (5 days per week for up to 61 weeks).  Both sexes initially received 0, 40 or 80 mg/kg-bw per day of 1,2-dibromoethane but due to excessive mortality the exposure levels and the overall duration of the study were reduced.  In both sexes, there were significant increases in the incidence of squamous cell carcinoma of the forestomach in exposed groups (0/20 for both male and female controls, 45/50 for low-dose males, 33/50 for high-dose males, 40/50 for low-dose females, 29/50 for high-dose females). In males in the lowest dose group, there was a significant increase in the incidence of hemangiosarcomas of the circulatory system (0/20 controls, 11/50 low dose); after time-adjusted analysis in high-dose females, there was a significant increase in the incidence of hepatocellular carcinomas (0/20 controls, 5/25 high dose) (NCI, 1978).

Oral (gavage) carcinogenicity bioassay in mice: Mice were exposed to time-weighted average doses of 0, 62 or 107 mg/kg-bw per day (5 days a week for 53 weeks). There were significant increases in the incidence of squamous cell carcinomas of the forestomach (males: vehicle control, 0/20; low dose, 45/50; high dose, 29/49; females: 0/20, 46/49, 28/50) and in alveolar/bronchiolar adenomas (males: control, 0/20; high dose, 10/47; females: control, 0/20; low dose, 11/43) (NCI, 1978).

[Additional studies: Van Duuren et al. (1985) (drinking water) - evidence of carcinogencity was observed]

Inhalation carcinogenicity bioassay in rats: Rats were exposed by inhalation to 0, 77 or 308 mg/m³ (6 hours per day, 5 days per week, for 88-103 weeks). There were significant increases in the incidence of nasal cavity carcinomas at high doses (males: controls, 0/50; high dose, 21/50; females: controls, 0/50; high dose, 25/50) and adenocarcinomas at both doses (males: controls, 0/50; low dose, 20/50; high dose, 28/50; females: 0/50, 20/50, 29/50). There was a significant increase in the incidence of hemangiosarcomas of the circulatory system in the high-dose groups of both sexes (males: controls, 0/50; high dose, 15/50; females: controls, 0/50; high dose, 5/50). Female rats had a significantly increased incidence of mammary gland fibroadenomas (controls, 4/50; low dose, 29/50; high dose, 24/50), and the highest-dose females exhibited significant levels of alveolar/bronchiolar adenomas combined with carcinomas (controls, 0/50; high dose, 5/47). Male rats had a significant increase in the incidence of tunica vaginalis mesotheliomas at both doses (controls, 0/50; low dose, 7/50; high dose, 25/50) and nasal cavity adenomatous polyps at low doses (controls, 0/50; low dose, 18/50) (NTP, 1982).

Inhalation carcinogenicity bioassay in mice: Mice were exposed by inhalation to 0, 77 or 308 mg/m³ (6 hours per day, 5 days per week, for 78-103 weeks). There were significantly increased incidences of alveolar/bronchiolar carcinomas (males: control, 0/41; high dose, 19/46; females: control, 1/49; high dose, 37/50) and adenomas (males: controls, 0/41; high dose, 11/46; females: controls, 3/49; high dose, 13/50) in the highest-dose groups of both sexes. In dosed females, there was also a significantly increased incidence of hemangiosarcomas of the circulatory system (controls, 0/50; low dose, 11/50; high dose, 23/50), subcutaneous fibrosarcomas (controls, 0/50; low dose, 5/50; high dose, 11/50), nasal cavity carcinomas (controls, 0/50; high dose, 6/50) and mammary gland adenocarcinomas (controls, 2/50; low dose, 14/50; high dose, 8/50) (NTP, 1982).

[Additional studies: Stinson et al. (1981); Wong et al. (1982) - evidence of carcinogenicity was observed in both studies]

Dermal carcinogenicity bioassay in mice: Female mice were given 0, 25 or 50 mg/mouse in acetone, dermally, 3 times a week for 440-594 days. There was a significant increase in the incidence of benign lung papillomas at both dose levels (low dose, 24/30; high dose, 26/30) and a significant increase in the incidence of combined squamous cell papillomas and carcinomas at the highest dose level (Van Duuren et al., 1985).

Lowest non-neoplastic oral (gavage) effect level (rats) = 38 (male) and 37 (female) mg/kg-bw per day, based on hyperkeratosis and acanthosis of the forestomach in females, degenerative changes in the liver, cortical cell degeneration of the adrenal gland and an earlier onset of testicular atrophy in males (lowest dose tested, carcinogenic dose) (NCI, 1978)

[Additional studies: NCI (1978)]

Lowest non-neoplastic inhalation concentration (rats) = 77 mg/m³, based on toxic nephropathy in males, retinal atrophy and adrenal cortex degeneration in females and increases in hepatic necrosis in both sexes (lowest dose tested, carcinogenic dose NTP, 1982).

[Additional studies: Stinson et al. (1981); NTP (1982); Wong et al. (1982)]

Reproductive toxicity

Lowest oral (feed) LOEL (bulls) = 2 mg/kg-bw per day for 12 months (followed by 4 mg/kg-bw every 2 days for 10-12 months), based on reversible low sperm density, poor motility and altered spermatozoa morphology (Amir and Volcani, 1965)

[Additional studies: Shivanandappa et al. (1987); NCI (1978)]

Lowest inhalation LOEC (rats) = 77 mg/m³, based on testicular degeneration in males (NTP, 1982)

[Additional studies: Short et al. (1979) for reduced reproductive capability of male rats]

Developmental toxicity

Lowest inhalation LOEC (rats) = 51.2 mg/m³, based on decreased maternal body weight and improved rotorod performance and T-maze brightness discrimination acquisition in offspring (Smith and Goldman, 1983)

[Additional studies: Short et al. (1978)]

Genotoxicity and related endpoints: in vitro

GENE MUTATION

Positive results:

Salmonella typhimurium TA98 (+/-S9), TA100 (+/-S9), TA100(GSH-) (-S9, +GSH), TA100(GSTA1-1 or GST1-1) (-S9), TA100W(Str^r, 8AG^r) (-S9), TA102 (activation not specified), TA1530 (-S9), TA1535 (+/-S9),  TA1535(GST1-1) (-S9), TA2638(activation not specified)  G46 (-S9) BA13 (+/-S9) [Ames and Yanofsky (1971); Von Buselmaier et al. (1972); Brem et al. (1974); McCann et al. (1975); Rosenkranz (1977); Rannug and Beije (1979); Elliott and Ashby (1980); Shiau et al. (1980); Stolzenberg and Hine (1980); van Bladeren et al. (1980, 1981); Barber et al. (1981); Principe et al. (1981); Barber and Donish (1982); Moriya et al. (1983); Buijs et al. (1984); Dunkel et al. (1985); Kerklaan et al. (1983, 1985); Guobaitis et al. (1986); Tennant et al. (1986, 1987); Hughes et al. (1987); Zoetemelk et al. (1987); Ong et al. (1989); Roldán-Arjona et al. (1991); Zeiger et al. (1992); Simula et al. (1993); Novotná and Duverger-van Bogaert (1994); Thier et al. (1996); Watanabe et al. (1998)]

Escherichia coli WP2 (+/-S9), WP2/pKM101 (activation not specified), WP2 uvrA/pKM101 (activation not specified), CHY832 (-S9), 343/286 (+/-S9), K12 (+/-S9), KI201 (-S9), KI211 (-S9), uvrB5[Scott et al. (1978); Hemminki et al. (1980); Izutani et al. (1980); Moriya et al. (1983); Hayes et al. (1984); Mohn et al. (1984); Dunkel et al. (1985); Foster et al. (1988); Watanabe et al. (1998)]

Bacillus subtilis TKJ5211, TKJ6321 (+S9) [Shiau et al. (1980)]

Streptomyces coelicolor (-S9, spot test) [Principe et al. (1981)]

Aspergillus nidulans [Scott et al. (1978); Principe et al. (1981)]

Neurospora crassa ad-3 (forward mutation) [de Serres and Malling (1983)]

Tradescantia clone 02, 0106, 4430 [Sparrow et al. (1974); Nauman et al. (1976); Vant'Hof and Schairer (1982)]

Mouse L5178Y (+/-S9) [Clive et al. (1979); Tennant et al. (1986, 1987)]

Chinese hamster CHO-K1(+/-S9) [Tan and Hsie (1981); Brimer et al. (1982)]

Human cell line AHH-1, TK6 (-S9) [Crespi et al. (1985)]

Human cell line EUE (-S9) [Ferreri et al. (1983)]

Negative results:

Salmonella typhimurium TA 98 (+/-S9), TA100(+/-S9), TA1537 (+/-S9), TA1538 (+/-S9), E503 [Brem et al. (1974); Alper and Ames (1975); Shiau et al. (1980); Principe et al. (1981); Wildeman and Nazar (1982); Moriya et al. (1983); Dunkel et al. (1985); Tennant et al. (1986)]

Serratia marcescens a21 (-S9) [Von Buselmaier et al. (1972)]

Escherichia coli 343/113 (-S9) [Mohn et al. (1984)]

Streptomyces coelicolor (-S9, plate method) [Principe et al. (1981)]

UNSCHEDULED DNA SYNTHESIS

Positive results:

Rat hepatocytes [Williams et al. (1982); Tennant et al. (1986); Working et al. (1986)]

Rat spermatocytes [Working et al. (1986)]

Opossum lymphocytes [Meneghini (1974)]

Human lymphocytes (+/-S9) [Perocco and Prodi (1981)]

Mouse (C3Hfx101)F1 germ cells [Sega and Rene (1980)]

SISTER CHROMATID EXCHANGE

Positive results:

Fish lymphocytes (-S9) [Ellingham et al. (1986)]

Chinese hamster V79 cl-15 (-S9) [Tezuka et al. (1980)]

Chinese hamster CHO (+/-S9) [Tennant et al. (1987); Ivett et al. (1989)]

Human lymphocytes (-S9) [Tucker et al. (1984); Ong et al. (1989)]

CHROMOSOME ABERRATIONS

Positive results:

Fish lymphocytes (-S9) [Ellingham et al. (1986)]

Chinese hamster V79 cl-15 (-S9) [Tezuka et al. (1980)]

Chinese hamster CHO (+/-S9) [Tennant et al. (1987); Ivett et al. (1989)]

MICRONUCLEI INDUCTION

Positive results:

Tradescantia clone 03, 4430 [Ma et al. (1978, 1984)]

Human lymphocytes [Channarayappa et al. (1992)]

DNA DAMAGE

Positive results:

Escherichia coli polA1-/polA+(-S9) [Brem et al. (1974)]

Negative results:

Bacilis subtilis TKJ5211, TKJ6321 (+/-S9) [Shiau et al. (1980)]

SOS INDUCTION

Positive results:

Salmonella typhimurium TA1535/pSK1002 (+/-S9), NM5004 expressing GST 5-5 [Ong et al. (1987); Oda et al. (1996)]

Escherichia coli [Ohta et al. (1984); Quillardet et al. (1985)]

Negative results:

Salmonella typhimurium TA1535/pSK1002 (-S9) [Oda et al. (1996)]

MITOTIC GENE CONVERSION

Positive results:

Saccharomyces cerevisiae ade2, trp5 [Fahrig (1974)]

SOMATIC SEGREGATION

Positive results:

Aspergillus nidulans diploid 35x17 (-S9) [Crebelli et al. (1984)]

CELL PROLIFERATION

Positive results:

Human lymphocytes [Channarayappa et al. (1992)]

DNA STRAND BREAKS

Positive results:

Rat hepatocytes [Sina et al. (1983)]

Rat testicular cells [Bradley and Dysart (1985)]

Rat and human testicular cells [Bjørge et al. (1996)]

DNA BINDING

Positive results:

Calf thymus DNA [Arfellini et al. (1984); Colacci et al. (1985); Prodi et al. (1986)]

Rat hepatocytes [Inskeep et al. (1986); Cmarik et al. (1990)]

Human hepatocytes [Cmarik et al. (1990)]

Negative results:

Escherichia coli Q13 (+/-S9) and mouse Ehrlich ascites (+/-S9) [Kubinski et al. (1981)]

CELL TRANSFORMATION

Positive results:

Balb/c 3T3 mouse cells [Perocco et al. (1991); Colacci et al. (1995)]

Negative results:

Balb/c 3T3 mouse cells (-S9) [Tennant et al. (1986)]

Genotoxicity and related endpoints: in vivo

GENE MUTATION

Positive results:

Drosophila melanogaster [Graf et al. (1984); Ballering et al. (1993)]

Salmonella typhimurium G46 host-mediated [Von Buselmaier et al. (1972)]

Barley [Ehrenberg et al. (1974)]

Negative results:

Serratia marcescens host-mediated [Von Buselmaier et al. (1972)]

Silk worm [Sugiyama (1980)]

RECOMBINATION

Positive results:

Drosophila melanogaster [Graf et al. (1984); Ballering et al. (1993)]

SEX-LINKED RECESSIVE LETHAL MUTATIONS

Positive results:

Drosophila melanogaster [Vogel and Chandler (1974); Kale and Baum (1979a,b, 1981, 1982, 1983); Yoshida and Inagaki (1986); Ballering et al. (1993, 1994); Foureman et al. (1994); Kale and Kale (1995)]

CHROMOSOME ABERRATIONS

Positive results:

Barley root tips [Ehrenberg et al. (1974)]

Negative results:

Mouse (intraperitoneal) bone marrow [Krishna et al. (1985)] (IARC reports weakly positive)

Mouse (intraperitoneal) bone marrow [National Toxicology Program Database (1993)]

DNA STRAND BREAKS

Positive results:

Rat hepatocytes [Nachtomi and Sarma (1977); Kitchin and Brown (1994)]

Mouse hepatocytes [White (1982); Storer and Conolly (1983)]

Rat testicular cells [Bradley and Dysart (1985)]

MICRONUCLEI

Positive results:

Mouse (peripheral blood) [Witt et al. (2000)]

Various amphibians [Fernandez et al. (1993)]

Tradescantia [Ma et al. (1978)]

Negative results:

Mouse [Krishna et al. (1985); Asita et al. (1992)]

DNA BINDING

Positive results:

Mouse (liver, stomach, kidney, lung) [Arfellini et al. (1984); Prodi et al. (1986)]

Mouse hepatocyte DNA [Kim & Guenguerich (1990)]

Rat (liver, stomach, kidney, lung) [Arfellini et al. (1984); Prodi et al. (1986)]

Rat hepatocyte DNA [Inskeep et al. (1986);  Kim & Guenguerich (1990)]

SPECIFIC LOCUS TEST

Negative results:

Mouse [Russell (1986); Barnett et al. (1992)]

SISTER CHROMATID EXCHANGE

Negative results:

Mouse (intraperitoneal) bone marrow [Krishna et al. (1985)]

Mouse (intraperitoneal) bone marrow [National Toxicology Program Database (1992)]

DOMINANT LETHAL

Negative results:

Rat [Short et al. (1979); Teramoto et al. (1980); Teaf et al. (1990)]

Mouse [Epstein et al. (1972); Teramoto et al. (1980); Barnett et al. (1992)]

DNA REPAIR EXCLUSIVE OF UNSCHEDULED DNA SYNTHESIS

Negative results:

Mouse hepatocytes [White et al. (1981)]

UNSCHEDULED DNA SYNTHESIS

Positive results:

Rat hepatocytes [Working et al. (1986)]

Negative results:

Rat spermatocytes [Working et al. (1986);  Bentley and Working (1988)]

DNA DAMAGE

Positive results:

Mouse (stomach, liver, kidney, bladder, lung) [Sasaki et al. (1998)]

Acute toxicity

Estimated oral lethal dose (human) = 200 mg/kg-bw, based on an observation that a 60-kg woman died from ingesting 12 g of 1,2-dibromoethane (Alexeeff et al., 1990)

Estimated inhalation lethal concentration (human) = 154 mg/m³ for more than 30 minutes (IPCS, 1996)

[Additional studies: Peoples et al. (1978); Letz et al. (1984); Jacobs (1985); Sarawat et al. (1986); Singh et al. (1993); Prakash et al. (1999); Raman and Sain (1999); Mehrotra et al. (2001)]

Chronic toxicity/ carcinogenicity

Mortality assessed in employees who were exposed to 1,2-dibromoethane in two production units (level of exposure was not provided in secondary accounts). In the first production unit, there were 2 deaths from malignant neoplasms (3.6 expected), and in the second production unit, there were 5 deaths from malignant neoplasms (2.2 expected). However, employees of the second production unit were also exposed to other chemicals, and overall there was no increase in total deaths or malignant neoplasms with increased exposure (Ott et al., 1980).

[Additional studies: Ter Haar (1980)]

Reproductive and developmental toxicity

Lowest inhalation LOEC = 0.46 mg/m³ (occupational time-weighted average in conjunction with dermal exposure) in male forestry workers, based on significantly decreased sperm velocity and semen volume (Schrader et al., 1988)

[Additional studies: Ter Haar (1980); Wong et al. (1985); Dobbins, (1987); Ratcliffe et al. (1987); Schrader et al. (1987)]

Genotoxicity and related endpoints

Negative results:

Chromosomal aberrations and sister chromatid exchange were not detected in workers exposed to mean concentrations ranging from 0.12 to 1.35 mg/m³ (Steenland et al., 1986).

[Additional studies: Steenland et al. (1985)]