Registration Dossier

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1960

Materials and methods

Principles of method if other than guideline:
Determination of the maximum single exposure resulting in no detectable organic injury.
GLP compliance:
no
Type of method:
in vivo
Endpoint addressed:
acute toxicity: inhalation

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): bromochloromethane
- Analytical purity: >99%

Test animals

Species:
rat
Strain:
not specified
Sex:
female

Administration / exposure

Route of administration:
inhalation: vapour
Vehicle:
unchanged (no vehicle)
Details on exposure:
CHAMBER DESCRIPTION: 160-liter capacity glass-walled chamber.
The exposures were made by introducing the groups of rats into established vapour concentrations by quickly dropping them through entry tubes on the top of the chambers.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Concentrations were checked from time to time before and during exposure by combustion analysis. The results were generally within 10% of the calculated values.
Duration of treatment / exposure:
From 0.1 h to 7 h.
Frequency of treatment:
Single exposures.
Post exposure period:
Animals were killed the following day of exposure.
Doses / concentrations
Remarks:
Doses / Concentrations:
600, 800, 1500, 5000, 10000 and 40000 ppm.
Basis:
nominal conc.
No. of animals per sex per dose:
Control groups: between 8 and 10 rats/group.
Treated groups: between 4 and 5 rats/group.
Control animals:
yes, concurrent no treatment

Examinations

Examinations:
- Necropsy of survivors performed: yes. After exposure, the exposed and control rats were killed in a fasted condition by decapitation. Gross pathological examination was made.
- Other examinations performed: organ weights and histopathology. After gross observation, the lungs, heart, liver, kidneys and spleen were removed and weighed. Portions of these organs, as well as the pancreas and adrenals were fixed in formalin and stained with hematoxylin-cosin for microscopic examination. In addition to the hematoxylin-eosin stain, a special fat stain, Oil Red O, was used on many of the sections.
Positive control:
None.

Results and discussion

Details on results:
- Gross pathology: No significant gross pathological changes were seen.
- Organ weights: increases in organ weights were seen in the kidney and the liver. SIgnificant increases in liver weight ofter accompanied histopathological changes of this organ.
- Histopathology: microscopic evidence of organic injurywas detected only in the liver. The degree of injury was slight being characterized by very small vacuoles distributed throughout the parenchyma but not typical of fatty degeneration.

Any other information on results incl. tables

Table 1. Summary of Single Vapour Exposures of Female Rats to Bromochloromethane (CH2BrCl) to Determine Organic Injury.

Calc. vapour conc. ppm

Dur. Of exp. (h)

No. of rats

Control

group*

Average body weight (g)

Average Organ Weights,

g/100 g body weight

Histopathology

Before exposure

Starved

Lung

Heart

Liver

Kidney

Spleen

Liver

Kidney

0

0

8

Series A

145

138

0.76

0.43

3.08

0.83

0.43

N

N

0

0

10

Series B

142

134

0.85

0.47

3.36

0.90

0.47

N

N

0

0

10

Series C

149

140

0.81

0.46

2.92

0.86

0.26

N

N

40,000

0.1

4

A

138

131

0.82

0.49

3.76b

0.93b

0.38

+

N

40,000

0.05

4

A

140

138

0.88

0.47

3.52a

0.88

0.36

¼ ±

N

40,000

0.025

5

C

145

136

0.74

0.47

2.84

0.87

0.27

N

N

10,000

0.7

4

A

157

149

0.73

0.45

3.81b

0.91a

0.46

+

N

10,000

0.4

4

A

151

142

0.77

0.46

3.60b

0.91

0.61

±

N

10,000

0.2

4

A

147

138

0.86

0.47

3.38a

0.87

0.48

2/4±

N

10,000

0.1

5

B

145

127

0.81

0.49

3.32

0.89

0.37

N

N

10,000

0.05

5

B

136

126

0.87

0.50

3.32

0.94

0.34

N

N

5,000

7.0

4

A

156

137

0.99

0.50

4.38c

1.01b

0.39

+

±

5,000

0.5

5

B

136

127

0.88

0.48

3.56

0.91

0.49

¼ ±

N

5,000

0.3

5

B

146

138

0.95

0.46

3.47

0.93

0.46

N

N

5,000

0.2

5

B

136

128

0.77

0.48

3.23

0.92

0.53

N

N

5,000

0.1

5

B

139

130

0.77

0.48

3.23

0.92

0.50

N

N

1,500

7.0

4

A

146

136

0.85

0.50

3.60a

0.91a

0.40

+

N

1,500

3.0

5

C

147

139

0.75

0.47

3.04

0.87

0.26

N

N

1,500

2.0

5

C

146

137

0.79

0.47

3.11

0.88

0.30

N

N

1,500

1.5

5

C

147

138

0.78

0.46

2.88

0.86

0.26

N

N

800

7.0

4

A

154

143

0.77

0.45

3.36

0.85

0.41

±

N

600

7.0

5

C

151

140

0.70

0.45

2.86

0.90

0.26

N

N

* Since exposures were made in three series (A, B, C), each series has its own set of controls.

a = P = 0.01 to 0.05; b = P = 0.001 to 0.01; c = P = <0.001; N = normal when compared to controls; ± = questionable response; + = Very slight; ++ = Slight; +++ = Moderate; ++++ = Severe; +++++ = Very severe.

Applicant's summary and conclusion

Conclusions:
The maximum exposures judged to be without detectable organic changes were 0.025 hour at 40,000 ppm; 0.1 hour at 10,000 ppm; 0.3 hour at 5,000 ppm; 3 hours at 1,500 ppm; and 7 hours at 600 ppm.
Executive summary:

In the present study, female rats were used to determine the maximum single exposures to bromochloromethane resulting in no detectable organic injury. The animals were exposed by inhalation to 600, 800, 1500, 5000, 10000 and 40000 ppm of bromochloromethane, from 0.1 to 7 hours. The exposed rats, as well as the control groups, were exposed after exposure and were subjected to a gross pathological examination. The lungs, heart, liver, kidneys and spleen were weighed and examinated microscopically. No significant gross pathological changes were ween. Microscopic evidence of organic injury was detected only in the liver although increases in organ weights were also seen in the kidney. The degree of injury was slight being characterized by very small vacuoles distributed throughout the parenchyma but not typical of fatty degeneration. Significant increases in liver weight often accompanied histopathological changes of this organ. The maximum exposures to bromochloromethane judged to be without detectable organic changes were 0.025 hour at 40,000 ppm; 0.1 hour at 10,000 ppm; 0.3 hour at 5,000 ppm; 3 hours at 1,500 ppm; and 7 hours at 600 ppm.