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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
combined repeated dose and carcinogenicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1967
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, but test conditions and results not sufficiently detailed.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1967

Materials and methods

Principles of method if other than guideline:
Combined chronic toxicity/carcinogenicity studies
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sodium arsenate

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
2 years
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
400, 250, 125, 62.5 and 31.25 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
50 animals/sex/dose
Control animals:
yes, concurrent no treatment

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
31.25 - 400 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Overall effects: Decreased survival, weight depression and enlargement of common bile duct
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

- Marked enlargement of the common bile duct in 25 and 42 animals at 250 and 400 ppm, respectively. These levels also caused weight depression and decreased survival.

- At 250 ppm, survival was slightly reduced, enlargement of the common bile duct (less pronounced) and reduced weight, particularly in females

- At 125, 62.5 and 31.25 ppm, arsenate did not cause common bile duct enlargement and did not affect survival. Body weight was slightly reduced in both sexes at 125 ppm

- No carcinogenic effect could be detected.

- Histopathologically, enlarged common bile ducts showed hyperplasia of the glandular elements, focal necrosis, and fibrosis.

Table 1: Weight and mortality of male and female rats fed sodium arsenate

Arsenic in dieta(ppm)

Duration of experiment (weeks)

Male

Female

Mean weight ± SE (g)

Cumulative mortality

Mean weight ± SE (g)

Cumulative mortality

Control

12

409 .7 ± 9.31

0

238.5 ± 6.58

0

27

518.4 ± 10.86

0

292.7 ± 6.01

0

52

550 .0 ± 15.11

0

338.9 ± 8.01

1

78

580.4 ± 18.22

5

332.5 ± 13.46

4

104

489.0 ± 28.31

15

395.4 ± 24.40

17

31.25

12

411.2 ± 9.59

0

236.2 ± 4.18

0

27

528.5 ± 14.70

2

283.5 ± 6.95

0

52

557.8 ± 19.76

2

325.5 ± 8.72

1

78

562.1 ± 25.60

7

352.4 ± 12.26

6

104

440.7 ± 33.97

18

320.5 7 21.71

18

62.5

12

401.0 ± 7.56

0

230.5 ± 3.68

0

27

508.6 ± 9.66

0

286.8 ± 5.61

0

52

540 .5 ± 12.39

1

336.1 ± 7.85

0

78

574 .1 ± 16.15

4

365.0 ± 14.04

3

104

497.4 ± 28.50

14

345.8 ± 28.81

18

125

12

375.5 ± 6.00

0

228.7 ± 4.12

0

27

491.4 ± 9.24

0

258.4 ± 7.17

1

52

542.4 ± 18.19

5

313.6 ± 10.09

2

78

520.4 ± 36.67

7

321.8 ± 15.67

7

104

465.2 ± 26.90

15

310.6 ± 25.40

18

250

12

348.5 ± 6.09

0

205.4 ± 2.81

0

27

463.1 ± 10.25

1

250.0 ± 4.54

0

52

528.4 ± 16.18

3

285.0 ± 7.49

4

78

541.5 ± 23.27

10

285.9 ± 19.45

10

104

454.4 ± 27 .09

17

294.0 ± 63.51

20

400

12

245.0 ± 9.49

1

167.0 ± 4.84

1

27

305.8 ± 10.91

3

215.6 ± 4.77

1

52

420.9 ± 14.21

8

240.2 ± 7.71

5

78

443.9 ± 19.85

14

269.6 ± 8.98

8

104

414.6 ± 30.44

20

246.0 ± 13.62

21

a There were 25 animals in each group at the start

Applicant's summary and conclusion

Conclusions:
Under the test conditions, sodium arsenate had the effect on survival, weight depression and common bile duct enlargement in Osborne-Mendel rats.
Executive summary:

In a 2 year study, sodium arsenate was administered through feed to groups of 50 weanling Osborne-Mendel rats/sex/dose at 400, 250, 125, 62.5 and 31.25 ppm. Mean starting body weight of male groups and female groups were 44 -46 g and 43 -45 g, respectively. Hematologic examinations were made on 10 males and 10 females from each group, after 3, 11, 17 and 22 months of the experiment. Body weights were recorded weekly. During 104th week of the feeding tests, animals from the appropriate groups were subjected to gross necropsy during which weights of heart, liver, spleen, kidney and testes were recorded. Histopathology was performed.

Slight increase of leukocyte count in the females at the highest dosage throughout the experiment and in the males for the first year. No distinct differences in ratio of organ weight to body weight were noted. Marked enlargement of the common bile duct was observed at 250 and 400 ppm and these levels also caused weight depression and decreased survival. At 250 ppm, survival was slightly reduced, enlargement of the common bile duct (less pronounced) and reduced weight, particularly in females was observed.At125, 62.5 and 31.25 ppm, arsenate did not cause common bile duct enlargement and did not affect survival. Body weight was slightly reduced in both sexes at 125 ppm. No carcinogenic effect could be detected. Histopathologically, enlarged common bile ducts showed hyperplasia of the glandular elements, focal necrosis and fibrosis.

Under the test conditions, sodium arsenate had the effect on survival, weight depression and common bile duct enlargement in Osborne-Mendel rats.