Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
other: clinical observation
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Sprematogenesis and reproductive performance following human accidantal exposure to bromine vapor.
Author:
Potashnik G, Carel R, Belmaker I and Levine M
Year:
1992
Bibliographic source:
Reproductive Toxicology 6: 171-174

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Spermatogensis and reproductive performance amongst 8 men and their spouses was evaluated following accidental exposure to bromine vapour.
GLP compliance:
no
Type of method:
other: clinical observations of exposed human males

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
other: Human
Sex:
male

Administration / exposure

Route of administration:
inhalation: vapour
Details on exposure:
Eight men were exposed to high concentrations of bromine vapour following accidental release in a road accident.
A truck loaded with 22,000 kg bromine liquid packed in 1 litre glass bottles overturned releasing 5000 kg of bromine into the environment to form a dense brownish-red cloud with well deined margins. No quantitative measurements were taken at the site. Nine men were involved in rescuing the driver of the truck which lasted about 4 hours. The driver died of severe respiratory distress caused by bromine intoxication.
Only eight of the men exposed consented to the fertility evaluation.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Approximately 4 hours
Frequency of treatment:
Not applicable
Duration of test:
Not applicable
No. of animals per sex per dose:
8 males

Results and discussion

Effect levels

Dose descriptor:
other: reproductive effect
Effect level:
other: Immediate Danger to life and Health (IDLH) level
Based on:
element
Sex:
male
Basis for effect level:
other: Mild degree of spermatogenic suppression and impaired reproductive performance

Observed effects

Acute exposure to bromine vapour caused a mild degree of spermatogenic suppression with no impairment of the hypothalamic - pituitary-testicular axis.
Altered sperm parameters and altered vibilities from bomine-induced sperm abnormalities could not be established.

Any other information on results incl. tables

Table 1: Semen analysis, hormonal profile, and reproductive history of 8 men accidentally exposed to bromine vapour.

Subject No.

Exposure time

(min)

Previous pregnancy in spouse (N)

Study interval (wks)

Semen analysis

Plasma bromine levels

Sperm density (x106/mL)

1-h motility (%)

Normalforms (%)

FSH (mIU/mL)

LH

(mIU/mL)

T

(mIU/mL)

1

240

2

9

2b

10

20

6.0

6.0

3.6

2

90

2

9

12

15

35

6.0

5.0

5.5

3

150

3

28

13

50

45

2.0

7.0

9.3

4

50

2

9

35

50

55

4.0

3.0

5.0

5

90

1

24

140

65

55

4.0

4.0

2.7

7

50

4

9

95

60

50

5.0

5.0

2.0

8

60

1

40

65

55

50

3.0

5.0

6.6

aFrom exposure to performance of tests

bSevere OTA had been diagnosed prior to the accident.

 

Table 2: Outcome of pregnancies conceived following accidental paternal exposure to bromine vapour.

Subject No.

Age of spouse (yr)

Sperm density (x106/mL)

Conception timea(wks)

Outcome of pregnancy

2

29

12

5

Complete abortion at 4 weeks

3

33

13

15

Spontaneous abortion at 16 weeks

4

32

35

2

Induced abortion at 8 weeks

5

30

140

9

Term normal female, 3450

8

32

65

14

Term normal male, 3300

aFrom paternal exposure to first missed period in spouse.

Applicant's summary and conclusion

Conclusions:
The study was undertaken to evaluate spermatogenesis and reproductive performance among 8 men and their spouses following accidental exposure to bromine vapour. Of the three cases with oligo-terato-asthenozospermia (OTA), one had been diagnosed prior to and unrelated to the event. Mild OTA and unimpaired reproductive performance characterised the other two cases. Plasma levels of the follicle stimulating hormone and luteinising hormone were normal in all men. One first-trimester abortion and one late abortion (due to chorioamnionitis) occurred among the 5 pregnancies conceived shortly after the accident. Results of the present study suggest a mild degree of spermatogenic suppression and impaired reproductive performance following paternal exposure to bromine vapour during the described incident. However, due to the small size of the study cohort, a confidential cause-result could not be established.
Executive summary:

The study was undertaken to evaluate spermatogenesis and reproductive performance among 8 men and their spouses following accidental exposure to bromine vapour. Of the three cases with oligo-terato-asthenozospermia (OTA), one had been diagnosed prior to and unrelated to the event. Mild OTA and unimpaired reproductive performance characterised the other two cases. Plasma levels of the follicle stimulating hormone and luteinising hormone were normal in all men. One first-trimester abortion and one late abortion (due to chorioamnionitis) occurred among the 5 pregnancies conceived shortly after the accident. Results of the present study suggest a mild degree of spermatogenic suppression and impaired reproductive performance following paternal exposure to bromine vapour during the described incident. However, due to the small size of the study cohort, a confidential cause-result could not be established.