Arsenic acid

Repeated dose toxicity: oral

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

Disodium hydrogenarsenate

EC Number:

231-902-4

EC Name:

Disodium hydrogenarsenate

Cas Number:

7778-43-0

IUPAC Name:

disodium hydrogen arsenate

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 diet^a(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.