13 BCP Toxicity

26
 I U C L I D  D a t a s e t Existing Chemical Substance ID: 109–70–6 CAS No. 109–70–6 EINECS Name 1–bromo–3–chloropropane EINECS No. 203–697–1  Molecular F ormula C3H6BrCl Dataset created by: EUROPEAN COMMISSION – European Chemicals Bureau This dossier is a compilation based on data reported by the European Chemicals Industry following ’Council Regulation (EEC) No. 793/93 on the Evaluation and Control of the Risks of Existing Substances’.  All (non–co nfidential) information from the si ngle datase ts, submitte d in the IUCLID/HEDSE T format by individual companies, was integrated to create this document. The data have not undergone any evaluation by the European Commission. Creation date: 18–FEB–2000  Number of P ages: 25 Chapters: all Edition: Year 2000 CD–ROM edition Flags: non–confidential  (C) 2000 EUROPEAN COMMISSION  European Chemicals Bureau

Transcript of 13 BCP Toxicity

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 1/26

I U C L I D

D a t a s e t

Existing Chemical Substance ID: 109–70–6

CAS No. 109–70–6EINECS Name 1–bromo–3–chloropropaneEINECS No. 203–697–1

Molecular Formula C3H6BrCl

Dataset created by: EUROPEAN COMMISSION – European Chemicals Bureau

This dossier is a compilation based on data reported by the EuropeanChemicals Industry following ’Council Regulation (EEC) No. 793/93on the Evaluation and Control of the Risks of Existing Substances’.

All (non–confidential) information from the single datasets, submitted in the IUCLID/HEDSET format by individual companies, was integrated to create this document.

The data have not undergone any evaluation by the European Commission.

Creation date: 18–FEB–2000

Number of Pages: 25

Chapters: all

Edition: Year 2000 CD–ROM edition

Flags: non–confidential

(C) 2000 EUROPEAN COMMISSION European Chemicals Bureau

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 2/26

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 3/26

date: 18–FEB–20001. General Information Substance ID: 109–70–6

______________________________________________________________________________

1.8 Occupational Exposure Limit Values

Type of limit: Limit value:Remark: No data of OEL values availableSource: Orion–Yhtymä Oy, Fermion Espoo

1.9 Source of Exposure–

1.10.1 Recommendations/Precautionary Measures–

1.10.2 Emergency Measures–

1.11 Packaging–

1.12 Possib. of Rendering Subst. Harmless–

1.13 Statements Concerning Waste–

1.14.1 Water Pollution–

1.14.2 Major Accident Hazards–

1.14.3 Air Pollution–

1.15 Additional Remarks

Remark: This material must be considered as a hazardous waste or material. Therefore, it must be disposed of in a "permitted" hazardous waste facility in compliance with national and/or local regulations. It should be handled in a manner acceptable to good waste management practice. Incineration is the recommended method of disposal.Source: ALBEMARLE PPC S.A. THANN

1.16 Last Literature Search–

– 2/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 4/26

date: 18–FEB–20001. General Information Substance ID: 109–70–6

______________________________________________________________________________

1.17 Reviews–

1.18 Listings e.g. Chemical Inventories–

– 3/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 5/26

date: 18–FEB–20002. Physico–chemical Data Substance ID: 109–70–6

______________________________________________________________________________

2.1 Melting Point

Value: ca. –59 degree C Method: other

Year: 1989 GLP: no dataSource: ALBEMARLE PPC S.A. THANN (1)

Value: –58.9 degree C Method: other

Year: 1979 GLP: no dataSource: ALBEMARLE PPC S.A. THANN (2)

Value: = –58.9 degree CSource: Orion–Yhtymä Oy, Fermion Espoo

2.2 Boiling Point

Value: ca. 141 degree C Method: other

Year: 1989 GLP: no dataSource: ALBEMARLE PPC S.A. THANN (1)

Value: = 143.3 degree CSource: Orion–Yhtymä Oy, Fermion Espoo

Value: 143.4 degree C at 1012.32 hPa Method: other

Year: 1979 GLP: no dataSource: ALBEMARLE PPC S.A. THANN (3)

2.3 Density

Type: density Value: ca. 1.5969 g/cm3 at 20 degree C Method: other

Year: 1979 GLP: no dataSource: ALBEMARLE PPC S.A. THANN (4)

Type: density Value: = 1.6 g/cm3 at 20 degree C

Source: Orion–Yhtymä Oy, Fermion Espoo

2.3.1 Granulometry–

– 4/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 6/26

date: 18–FEB–20002. Physico–chemical Data Substance ID: 109–70–6

______________________________________________________________________________

2.4 Vapour Pressure

Value: ca. 12.987 hPa at 32 degree C Method: other (measured)

Year: 1989 GLP: no dataSource: ALBEMARLE PPC S.A. THANN (1)

Value: = 13.3 hPa at 32.4 degree C Method: other (measured)

Source: Orion–Yhtymä Oy, Fermion Espoo

2.5 Partition Coefficient–

2.6.1 Water Solubility

Value: = 0Source: Orion–Yhtymä Oy, Fermion Espoo

2.6.2 Surface Tension–

2.7 Flash Point

Value: = 57 degree CType:

Method: other Year:Remark: DIN 51755Source: Orion–Yhtymä Oy, Fermion Espoo

2.8 Auto Flammability–

2.9 Flammability–

2.10 Explosive Properties

Result: otherRemark: 3.2 vol–% / 8.6 vol–%Source: Orion–Yhtymä Oy, Fermion Espoo

2.11 Oxidizing Properties–

– 5/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 7/26

date: 18–FEB–20002. Physico–chemical Data Substance ID: 109–70–6

______________________________________________________________________________

2.12 Additional Remarks–

– 6/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 8/26

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 9/26

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 10/26

date: 18–FEB–20004. Ecotoxicity Substance ID: 109–70–6

______________________________________________________________________________

AQUATIC ORGANISMS

4.1 Acute/Prolonged Toxicity to Fish

Type: staticSpecies: Carassius auratus (Fish, fresh water)Exposure period: 24 hour(s)Unit: µg/l Analytical monitoring: yesLC50: ca. 75000

Method: other: standard methods followed Year: 1979 GLP: no dataTest substance: no dataRemark: This study used goldfish averaging 3.3 grams in weight and 6.2 cm in length. Dissolved oxygen was recorded as greater than 4.0 mg/liter and the pH of the fresh (local tap) water used in the test was 7.0. Standard methods of the American

Public Health Association, 1971 for static tank acute toxicity tests were used. A volatile comment was made, thus aeration was minimized. LC50 was recorded as 75000 ug/liter.Source: ALBEMARLE PPC S.A. THANN (6)

Type: otherSpecies: Carassius auratus (Fish, fresh water)Exposure period: 24 hour(s)Unit: mg/l Analytical monitoring:LC50: = 75

Method: Year: GLP:Test substance:Source: Orion–Yhtymä Oy, Fermion Espoo

4.2 Acute Toxicity to Aquatic Invertebrates–

4.3 Toxicity to Aquatic Plants e.g. Algae–

4.4 Toxicity to Microorganisms e.g. Bacteria–

– 9/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 11/26

date: 18–FEB–20004. Ecotoxicity Substance ID: 109–70–6

______________________________________________________________________________

4.5 Chronic Toxicity to Aquatic Organisms

4.5.1 Chronic Toxicity to Fish–

4.5.2 Chronic Toxicity to Aquatic Invertebrates–

TERRESTRIAL ORGANISMS

4.6.1 Toxicity to Soil Dwelling Organisms–

4.6.2 Toxicity to Terrestrial Plants–

4.6.3 Toxicity to other Non–Mamm. Terrestrial Species

Species: other: Xenopus laevisEndpoint: mortalityExpos. period: 48 hour(s)Unit: other: ug/lLC50: 41000

Method: other Year: 1987 GLP: no dataTest substance: no dataRemark: Three to four week clawed toads were used in this static study in fresh water. Temperature was maintained at 20 degrees C. Concentrations were not measured. LC50 was reported as 41000 ug/liter.Source: ALBEMARLE PPC S.A. THANN (7)

4.7 Biological Effects Monitoring–

4.8 Biotransformation and Kinetics–

4.9 Additional Remarks–

– 10/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 12/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

5.1 Acute Toxicity

5.1.1 Acute Oral Toxicity

Type: LD50Species: ratSex:

Number of Animals:

Vehicle: Value: 1100 – 1200 mg/kg bw Method: Directive 84/449/EEC, B.1 "Acute toxicity (oral)"

Year: 1993 GLP: yesTest substance: as prescribed by 1.1 – 1.4Remark: Groups of 10 (5 male, 5 female) Sprague Dawley rats were gavaged with a single dose of neat test article at either

0.8, 1.0, or 1.6 grams/kg body weight. There were deaths in male and female rats at 1.0 grams/kg and above. Deaths occurred within 4 hours to day 7. Slight body weight changes were noted in all animals that died. Macroscopic exam of animals that died revealed pale liver, dark spleen, and congested large intestine blood vessels in one male dosed at 1 gram/kilogram. One male and one female dosed at 1.6 grams/kilogram had slight congestion of the blood vessels of the glandular stomach, and the female also had congested intestinal vessels. Clinical signs included piloerection and increased salivation in all rats within 5 minutes. Other signs included hunched posture, waddling gait, lethargy, decreased respiratory rate, ptosis, pallor of extremities, swollen nictating membranes, ataxia, prostration, and body tremors. Surviving animals had normal external appearance and behavior by day 3 (0.8 g/kg) or day 4 (1.0 g/kg). At necropsy of surviving animals, one female had a pale mottled liver (0.8 g/kg). When a fixed slope of 8.2 was assumed, the acute median lethal dose for both sexes and it’s 95% confidence limts were estimated to be 1.1 (1.0 to 1.3) grams/kg body weight. Estimate for males alone was 1.1 (0.9 to 1.4) g/kg and for females alone was 1.2 (1.0 to 1.5 grams/kilogram body weight.

Source: ALBEMARLE PPC S.A. THANN (8)

– 11/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 13/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

Type: LD50Species: ratSex:

Number of Animals:

Vehicle: Value: 680 mg/kg bw Method: other

Year: 1979 GLP: no dataTest substance: no dataRemark: Five groups of ten rats (5 male, 5 female) were gavaged with test article at doses of 250, 625, 700, 775, and 1000 mg/kg body weight. Test article was carried in 0.25% methylcellulose. The 250 mg/kg dose group showed increased salivation and slight piloerection. The salivation was greater in the 650 mg/kg group. Overt symptomology was

present in higher dose groups. Mortality was 2 of 10 in the 635 mg/kg group, 5 of 10 in the 700 mg/kg group, and all of the rats in the 775 and 1000 mg/kg groups. Necropsy findings in some rats that died included reddened intestinges, and clear pleural fluid. LD50 was calculated by the method of Litchfield and Wilcoxon, 1949. Oral LD50 with 95% confidence limits was 680 mg/kg (621 to 745 mg/kg).Source: ALBEMARLE PPC S.A. THANN (9)

Type: LD50Species: ratSex:

Number of Animals:

Vehicle: Value: 930 – 1100 mg/kg bw Method: other

Year: 1971 GLP: no dataTest substance: no dataRemark: In short term experiments in female albino rats gavaged with test article, LD50 was found to be 1,100 (987–1227) mg/kg. LD16 was 940 mg/kg and LD84 was 1290 mg/kg. Most deaths occurred within two days. Clinical signs included depression, lack of activity progressing to muscular

weakness. Necropsy findings included congestion of internal organs and reduced thickness of gastric wall with hemorrhagic zones. Microscopic exam showed dystrophic changes of parenchymatous organs and congestion and edema of the stomach. Male rats had an LD50 of 930 mg/kg.Source: ALBEMARLE PPC S.A. THANN (10)

– 12/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 14/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

Type: LD50Species: ratSex:

Number of Animals:

Vehicle: Value: = 930 mg/kg bw Method:

Year: GLP:Test substance:Source: Orion–Yhtymä Oy, Fermion Espoo

Type: LD50Species: mouseSex:

Number of

Animals: Vehicle: Value: 1290 mg/kg bw Method: other

Year: 1982 GLP: no dataTest substance: no dataSource: ALBEMARLE PPC S.A. THANN (11)

5.1.2 Acute Inhalation Toxicity

Type: LC50Species: ratSex:

Number of Animals:

Vehicle:Exposure time: 60 minute(s)

Value: > 13.92 mg/l Method: other

Year: 1976 GLP: noTest substance: other TSRemark: Five male and five female Sprague Dawley rats were used in this acute inhalation study. An airstream containing a

saturated vapor of the test article was passed through a 26.5 liter test chamber containing the rats. The saturated vapor was generated by passing a 2 liter per minute airstream through a midget bubbler containing the test material. Total airflow through the chamber was 4 liters per minute. The bubbler was weighed before and after the exposure period of 60 minutes. A total of 3.34 grams of test material was delivered to give an overall nominal chamber concentration of 13.92 mg/liter at 1 atmosphere pressure and 23 degrees C. There were no deaths within 15 days. Clinical signs noticed during exposure were tearing and eye closure. This

behavior subsided after the exposure period. Other in–life observations included nasal discharge, wheezing, soft stool and urinary incontinence, but these effects varied in frequency and were not thought compound related. Body

– 13/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 15/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

weights and necropsy findings did not reveal test article related toxicity.Source: ALBEMARLE PPC S.A. THANN (12)

Type: LC50Species: ratSex:

Number of Animals:

Vehicle:Exposure time: 4 hour(s)

Value: 7.27 mg/l Method: other

Year: 1971 GLP: no dataTest substance: no data

Remark: An LC50 of 7.27 (7.00–7.55) mg/liter was determined in female albino rats inhaling vapors of test article for 4 hours. LC16 was 6.8 mg/liter and LC84 was 7.8 mg/liter. Concentration analysis of air samples was performed by the method of F.D. Krivoruchko (1967). Male rats had an LC50 of 6.5 mg/liter. Clinical signs were similar to those seen in the oral studies. Necropsy findings included congestion of internal organs and pulmonary hemorrhages. Microscopic examination revealed fatty degeneration of the liver and albuminoid degeneration of the kidneys. Congestion and irritation of the bronchial mucosa, fatty degeneration of the heart, and edema and swelling of neural tissue of the brain were seen.Source: ALBEMARLE PPC S.A. THANN (10)

Type: LC50Species: ratSex:

Number of Animals:

Vehicle:Exposure time:

Value: 5.668 mg/l Method: other

Year: 1975 GLP: no dataTest substance: no dataSource: ALBEMARLE PPC S.A. THANN (13)

– 14/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 16/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

Type: LC50Species: mouseSex:

Number of Animals:

Vehicle:Exposure time: 2 hour(s)

Value: 7.27 mg/l Method: other

Year: 1982 GLP: no dataTest substance: no dataRemark: No toxic effect noted.Source: ALBEMARLE PPC S.A. THANN (14)

Type:

Species:Sex:

Number of Animals:

Vehicle:Exposure time:

Value: Method:

Year: GLP:Test substance:Source: Orion–Yhtymä Oy, Fermion Espoo

5.1.3 Acute Dermal Toxicity

Type: LD50Species: ratSex:

Number of Animals:

Vehicle: Value: > 2000 mg/kg bw Method: other: EEC 84/449/EEC B.3

Year: 1992 GLP: yesTest substance: as prescribed by 1.1 – 1.4

Remark: A group of 10 rats (5 male, 5 female) were clipped of back hair over an area not greater than 10% of the total body surface. Neat test article was applied as a single application of 2.0 g/kg body weight to the intact skin under a dressing and was allowed to remain for 24 hours. Removal of test article was made with warm water. There were no deaths within 15 days of application. Increased locomotor activity and respiratory rate were seen immediately after dosing. Sites of application showed no irritation. Slightly lower body weight gains were noted on some days in some animals. No abnormalities were noted at necropsy.Source: ALBEMARLE PPC S.A. THANN

(15)

– 15/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 17/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

Type: LD50Species: rabbitSex:

Number of Animals:

Vehicle: Value: 3000 mg/kg bw Method: other: 16 CFR 1500.40

Year: 1977 GLP: no dataTest substance: other TSRemark: This acute dermal toxicity study used four New Zealand White rabbits per dose group. Hair was clipped over at least 30% of the body surface area, and two rabbits of each dose group had abrasions penetrating the stratum corneum prepared over the area of exposure. Dose groups were 2.0, 2.8, 4.0, and 5.7 grams/kg body weight. Test article was

applied under an impervious sleeve for 24 hours. After 24 hours, test article was wiped from the skin and dermal reactions scored. One animal of four died in the 2.0 and 2.8 grams/kg groups. All animals died at higher dose levels. Slight to moderate erythema and edema were noted in all animals at 24 hours. Clinical signs in the first 24 hours included ataxia and prostration. Muscle tremors were noted at 2.0 and 2.8 mg/kg. In the higher dose groups, tachypnea, corneal and conjunctival redness and dilation of the pupils were noted. All surviving animals were free of clinical signs by day 2. LD50 was estimated by means of logarithmic–probit graph paper (Miller and Tainter, 1944). LD50 with 95% confidence levels was 3000 grams/kilogram body weight (2.2 to 3.8 grams/kg).Source: ALBEMARLE PPC S.A. THANN (16)

5.1.4 Acute Toxicity, other Routes

Type: otherSpecies: mouseSex:

Number of

Animals: Vehicle:

Route of admin.: other: tail skinExposure time: 4 hour(s)

Value: Method: other

Year: 1971 GLP: no dataTest substance: no dataRemark: Four hour exposure of mice to test article via the tail did not cause deaths within a 14 day observation period. However, pronounced hyperemia of the tail skin was observed, progressing to necrosis on the second or third day,

followed by sloughing of the necrotic tissue.Source: ALBEMARLE PPC S.A. THANN (10)

– 16/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 18/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

5.2 Corrosiveness and Irritation

5.2.1 Skin Irritation

Species: rabbitConcentration:

Exposure:Exposure Time:

Number of Animals:PDII:Result: not irritatingEC classificat.: not irritating

Method: Directive 84/449/EEC, B.4 "Acute toxicity (skin irritation)" Year: 1992 GLP: yes

Test substance: as prescribed by 1.1 – 1.4Remark: Three rabbits were administered 0.5 ml of test article to the intact skin under a semiocclusive dressing for a period of 4 hours before removal of test article with warm water, and observed for 5 days. Reactions were very slight to well defined, but had resolved by day 5. Edema scores were "1" for all rabbits on days 3 and 4 and "0" at all other points. Mean redness scores were "0" on day 1, "0.67" on day 2, "2" on day 3, "1" on day 4 and "0" on day 5. It was concluded that the test article did not require labelling with risk phrase R38.Source: ALBEMARLE PPC S.A. THANN (17)

Species: rabbitConcentration:

Exposure:Exposure Time:

Number of Animals:PDII:Result:EC classificat.:

Method: other: FHSA 16 CFR 1500.41

Year: 1976 GLP: no dataTest substance: other TSRemark: Six New Zealand White rabbits were clipped of hair over the back and sides. Two test sites per rabbit were prepared, one site was abraded. Neat test material (0.5 ml) was applied under gauze on the test site, and the animals wrapped with an occlusive dressing. After 24 hours, the wrappings and gauze were removed. Mean erythema scores for intact and abraded skin were 1.17 at 24 hours and 1.0 at 72 hours. Mean edema scores for intact skin were 1.33 for 24 and 72 hour readings. Mean edema score for 24 hours on abraded skin was 1.83 and at 72 hours was 1.67.

Primary Dermal Irritation Index was 2.63.Source: ALBEMARLE PPC S.A. THANN (18)

– 17/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 19/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

5.2.2 Eye Irritation

Species: rabbitConcentration:Dose:Exposure Time:Comment:

Number of Animals:Result: not irritatingEC classificat.: not irritating

Method: Directive 84/449/EEC, B.5 "Acute toxicity (eye irritation)" Year: 1993 GLP: yesTest substance: as prescribed by 1.1 – 1.4Remark: Three rabbits were each administered a single ocular dose of 0.1 ml test substance and observed over a 7 day period.

Effects were temporary corneal opacity (one animal), transient dulling of the cornea (1 animal), transient iridial inflammation (one animal) and slight to well defined conjunctival irritation. All reactions had resolved in 7 days. Interpretation was that the test article did not require labelling with risk phrase R36.Source: ALBEMARLE PPC S.A. THANN (19)

Species: rabbitConcentration:Dose:Exposure Time:Comment:

Number of Animals:Result:EC classificat.:

Method: other: FHSA 16 CFR 1500.42 Year: 1976 GLP: no dataTest substance: other TSRemark: Six New Zealand White rabbits had 0.1 ml of test article instilled into the right eye without washout. Scoring for ocular reaction was done on days 1 to 4 and day 8. Five of six animals had positive scores for conjunctival irritation

at some reading. Corneal opacities were noted in three of these eyes. One eye had an ulceration of the nictitating membrane. All eyes were free of irritation by day 8. Maximum Draize score was a "30" in one animal. Mean Draize score was 17.Source: ALBEMARLE PPC S.A. THANN (20)

– 18/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 20/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

Species: rabbitConcentration:Dose:Exposure Time:Comment:

Number of Animals:Result:EC classificat.:

Method: other Year: 1971 GLP: no dataTest substance: no dataRemark: When applied to the mucosa of rabbit eyes, test article caused pronounced redness and purulent conjunctivitis that cleared in 4 days.Source: ALBEMARLE PPC S.A. THANN

(10)

5.3 Sensitization–

5.4 Repeated Dose Toxicity

Species: rat Sex:Strain:Route of admin.: other: oral and inhalationExposure period:Frequency of treatment:Post. obs. period:Doses:Control Group:

Method: Year: GLP:Test substance:Remark: A "subchronic toxicity test" by the method of Lim et al. (1961) was conducted. There were no deaths in animals by the 24th day when animals had received 9 x LD50. During the

next 4 days, animals tolerated daily doses nearly as high as the LD50. Two concentrations (0.045 and 0.0054 mg/liter) were used in long term experiments using six animals per group. Various effects were seen from the high concentration: increased summation threshold index, decreased ability to eliminate sulfobromophthalein from the blood, and increased liver weight coefficients. Histologically, liver changes included moderate albuminoid and fatty degeneration of the parenchyma and focal proliferation of the interstitial tissue cells. Few effects were seen as a result of the lower concentration; histological effects were mild. After

a one–month recovery period, the residual pathological processes were hardly noticeable, and were of a proliferative nature. Anaphase analysis of bone marrow cells showed higher

– 19/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 21/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

number of chromosome aberrations in animals exposed to 0.45 mg/liter than in the control animals. Changes in germinal epithelium and a tendency towards reduction in testicular weight coefficient and spermatzoa motility time were noted. Degenerative changes were seen in spermatagonia and spermatazoa.Source: ALBEMARLE PPC S.A. THANN (10)

5.5 Genetic Toxicity ’in Vitro’

Type: Ames testSystem of testing: Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA100, and TA98

Concentration: 0.1 ul; 0.5 ul; 1.0ul; 5.0 ul; 10 ul of a 10% solution TA in DMSO

Metabolic activation: with and withoutResult: negative

Method: other: Ames et al. 1975 Year: 1978 GLP: no dataTest substance: other TSRemark: Test article for this study was a 10% (v/v) solution in DMSO. Five concentrations were tested in each strain. Concentrations tested in units per plate were 0.1 ul, 0.5 ul, 1.0 ul, 5.0 ul, and 10.0 ul. The 10 ul per plate concentration was toxic to TA 1537, TA 1538, and TA 98 in the assay without metabolic activation. Other concentrations were not toxic to any strain in either assay. Metabolic activation involved preparation of S–9 fraction from Aroclor 1254 induced adult male Sprague Dawley rats. Criteria for a valid test were met. The test agent did not induce a significant increase in the number of point mutations in Salmonella typhimurium strains in the presence of an exogenous source of liver enzymes for metabolic activation nor in the absence of the activating system for the strains TA 1535, TA1537, TA1538, TA100, and TA 98.Source: ALBEMARLE PPC S.A. THANN

(21)

– 20/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 22/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

5.6 Genetic Toxicity ’in Vivo’

Type: Dominant lethal assaySpecies: rat Sex: male/femaleStrain: Sprague–DawleyRoute of admin.: gavageExposure period: once daily, 5 days/week for 10 weeksDoses: 25 mg/kg; 75 mg/kg; and 125 mg/kg body weightResult:

Method: other: FDA modified Year: 1980 GLP: no dataTest substance: other TSRemark: Three groups of ten male Sprague Dawley rats were given test article orally at doses of 125, 75, and 25 mg/kg. Concurrently, triethylenemelamine was given as a positive control orally to a group of 10 male rats at a dose of 0.05

mg/kg. Vehicle control group of ten rats received 0.25% methylcellulose. Each substance was administered once daily for five days a week for ten consecutive weeks. After the final dose, each male was co–housed with two virgin females for seven days. The mating was repeated the following week for a total of two mating periods. The femaes were sacrificed at 14 days from the mid–week of co–housing and the number of the corpora lutea and live and dead implants recorded. The test article did not produce dominant lethal effects in the male rats at the doses administered as measured by pre–implantation and post–implantation losses. Dominant lethal effects were seen in the positive control group as a sinificant increase in post–implanatation deaths.Source: ALBEMARLE PPC S.A. THANN (22)

5.7 Carcinogenicity–

5.8 Toxicity to Reproduction

Type: other: testicular functionSpecies: mouse Sex: male

Strain: CD–1Route of admin.: gavageExposure Period: 5 consecutive daysFrequency of treatment: once daily for 5 daysDuration of test: six weeksDoses: 300, 600, 1200 mg/kg/dayControl Group: yes, concurrent vehicle

NOAEL Parental: 600 mg/kg bw Method:

Year: 1978 GLP: no dataTest substance: other TS

Remark: A testicular funtion study was conducted in Charles River CD–1 mice to evaluate the effects of test article on spermatogenesis. Sexually mature mice approximately 3 months of age at the start of the study were treated orally

– 21/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 23/26

date: 18–FEB–20005. Toxicity Substance ID: 109–70–6

______________________________________________________________________________

for 5 consecutive days with test article in corn oil at doses of 300, 600, or 1200 mg/kg body weight per day. A control group received 5 ml/kg of corn oil vehicle per day. After dosing, 1/6 of each group (4 treated and seven control rats) were sacrificed at the one week post treatment date. This process was repeated over the next five weeks. At sacrifice, a smear of the contents of the cauda epididymidis was examined for spermatazoa and testes weighed before fixing and histological exam. Twenty of the 24 mice in the 1200 mg/kg dose group died by the fifth dose. No effects attributable to treatment were observed in mice given 600 mg/kg body weight or less in the areas of clinical signs of toxicity, body weight, spermatogenesis or testicular morphology.Source: ALBEMARLE PPC S.A. THANN (23)

5.9 Developmental Toxicity/Teratogenicity–

5.10 Other Relevant Information

Type: other: testicular effectsRemark: Toxicity of 1–chloro–3–bromopropane was evaluated in male albino Wistar rats for testicular effects. The control group of 20 animals were given arachis oil vehicle. Test groups (10 per group) were exposed by gavage to 40 or 160 mg/kg/day of test article for 14 days. Animals were sacrificed on day 15 for pathological exam. No significant differences between control and treated animals were seen in body weights, body weight gains, testes weights, morphology or in detailed macroscopic and microscopic examination of the kidneys, testes, epididymides, ductuli efferentes, and vasa deferentes.Source: ALBEMARLE PPC S.A. THANN (24)

5.11 Experience with Human Exposure–

– 22/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 24/26

date: 18–FEB–20006. References Substance ID: 109–70–6

______________________________________________________________________________

(1) Rhone–Poulenc Inc. Material Safety Data Sheet, Princeton N.J., 1989.

(2) Weast, R.C., ed., Handbook of Chemistry and Physics, 60th edition, Boca Raton, Florida, CRC Press Inc., 1979

(3) Weast, R.C., ed., Handbook of Chemistry and Physics, 60th edition, Boca Raton, Florida: CRC Press Inc., 1979. C–446.

(4) Weast, R.C., ed., Handbook of Chemistry and Physics, 60th edition, Boca Raton, Florida. CRC Press, Inc., 1979.C–446.

(5) Bridie, A.L., Wolfe, C.J.M., and Winter, M. "BOD and COD of Some Petrochemicals," Water Research, 13, 627–630, 1979.

(6) Bridie, A.L., Wolff, C.J.M., Winter, M., "The Acute Toxicity

of Some Petrochemicals to Goldfish," Water Res. 13(7): 623–626. as reported in the AQUIRE database.

(7) DeZwart, D., and Sloof, W. "Toxicity of Mixtures of Heavy Metals and Petrochemicals to Xenopus laevis," Bull. Environ. Contam. Toxicol., 38(2):345–351, 1987 as cited in AQUIRE database.

(8) Rhone Poulenc, France, unpublished studies, "1–Bromo–3–chloropropane Acute Oral Toxicity to the Rat," conducted at Huntingdon Research Centre, 1993.

(9) Ethyl Corporation, unpublished data, "Acute Oral LD50 Determination in Rats," conducted at Pharmakon Laboratories, 1979

(10) Eytingon, A.I., "Characteristics of the General Toxic, Gonadatropic, and Mutagenic Effects of 1,3–chlorobromopropane," Toksikologiya Novykh Promyshlennykh Khimicheskikh Veshchestv, No. 12, pp 93–100, 1971.

(11) Registry of Toxic Effects of Chemical Substances, 1985–1986, citing Toxicometric Parameters of Industrial Toxic Chemicals Under Single Exposure, Moscow, 1982.

(12) Ethyl Corporation, unpublished data, "Acute Inhalation Study Compound TMCB," conducted by Bio/dynamics Inc., 1976.

(13) Registry of Toxic Effects of Chemical Substances, 1985–1986, citing Gigiena Truda i Professional’nye Zabolevaniia, USSR. 19 (9) 36, 1975.

(14) Registry of Toxic Effects of Chemical Substances, 1985–1986, citing Toxicometric Parameters of Industrial Toxic ChemicalsUnder Single Exposure, Moscow, 1982.

– 23/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 25/26

date: 18–FEB–20006. References Substance ID: 109–70–6

______________________________________________________________________________

(15) Rhone Poulenc, France, unpublished studies, "1–Bromo–3–chloropropane Acute Dermal Toxicity to the rat," conducted at Huntingdon Research Centre, 1992.

(16) Ethyl Corporation, unpublished data, "Acute Dermal Toxicity Study Compound TMCB," conducted by Bio/dynamics Inc., 1977.

(17) Rhone Poulenc, France, unpublished studies, "1–Bromo–3–chloropropane Skin Irritation to the Rabbit," conducted at Huntingdon Research Centre, 1992.

(18) Ethyl Corporation, unpublished data, "Primary Dermal Irritation Compound TMCB," conducted by Bio/dynamics Inc., 1976.

(19) Rhone Poulenc, France, unpublished studies,

"1–Bromo–3–chloropropane Eye Irritation to the Rabbit," conducted at Huntingdon Research Centre, 1993.

(20) Ethyl Corporation, unpublished data, "Rabbit Eye Irritation Study Compound TMCB," conducted by Bio/dynamics Inc., 1976.

(21) Ethyl Corporation, unpublished data, "Activity of TMCB in the Salmonella/Microsomal Assay for Bacterial Mutagenicity," conducted by Microbiological Associates, 1978.

(22) Ethyl Corporation, unpublished data, "Dominant Lethal Assay FDA Modified," conducted by Pharmakon Laboratories, 1980.

(23) Ethyl Corporation, unpublished data, "Effects from Five Days of Treatment on Testicular Function in Mice," conducted by International Research and Development Corporation, 1978.

(24) Tunstall Laboratory, Shell Oil Company, "Toxicity of Fine Chemicals: Preliminary Studies for the Detection of Testicular Changes in Rats," 1979 as reported in EPA Document 878216424, Fiche No. OTS0510352.

– 24/25 –

8/12/2019 13 BCP Toxicity

http://slidepdf.com/reader/full/13-bcp-toxicity 26/26

date: 18–FEB–20007. Risk Assessment Substance ID: 109–70–6

______________________________________________________________________________

7.1 Risk Assessment–