Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From June 26 to November 11, 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed similarly to OECD guideline 401 without any deviation
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Arsenic acid
- Physical state: Clear, green liquid
- Composition of test material, percentage of components: Arsenic acid 75% w/w
- Analytical purity: sponsor assumes responsibility for purity and stability determination
- Storage condition of test material: Room temperature

Test animals

Species:
mouse
Strain:
other: Crl:CD-1 (ICR) BR strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, MI, USA
- Age at study initiation: Young adult (ca. 8 weeks)
- Weight at study initiation: 18-25 g
- Fasting period before study: 4-5 hours
- Housing: Housed in groups of 5/sex in cages
- Diet (e.g. ad libitum): Purina Rodent Chow; ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23 °C
- Humidity (%): 53-64%
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw

DOSAGE PREPARATION: The test material was mixed with distilled water to form a uniform suspension at a specific concentration according to dose level.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Dose was selected based on a range-finding study conducted on 1 mouse/sex/dose at 4 dose levels.
Doses:
75, 100 and 200 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each animal was observed for clinical signs and mortality at 1, 2.5 and 4 hours after dosing and daily thereafter for 14 days for clinical signs and twice daily for mortality. Individual bodyweights were recorded on Days 0 (prior to dosing), 7 and 14 or at death.
- Necropsy of survivors performed: Yes
Statistics:
LD50 was estimated using a modified Behrens-Reed-Muench cumulant method (Thakur AK and Fazio WL, 1981).

Results and discussion

Preliminary study:
No data
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
141.4 mg/kg bw
Based on:
test mat.
95% CL:
>= 98.8 - <= 202.3
Sex:
female
Dose descriptor:
LD50
Effect level:
160.4 mg/kg bw
Based on:
test mat.
95% CL:
>= 107.1 - <= 240.3
Sex:
male/female
Dose descriptor:
LD50
Effect level:
149.6 mg/kg bw
Based on:
test mat.
95% CL:
>= 114.4 - <= 195.5
Mortality:
- At 75 mg/kg bw: No deaths
- At 100 mg/kg bw: 1/5 male and 1/5 female died on Day 1
- At 200 mg/kg bw: 4/5 males and 2/5 females died on Day 1; one female died on Day 3
Clinical signs:
Clinical signs noted were diarrhoea, hypoactivity, ataxia and tremors. All signs in surviving animals resolved completely by Day 4.
Body weight:
All animals showed expected gain in bodyweight over the study period.
Gross pathology:
- Necropsy of the surviving animals at 75 mg/kg bw revealed stomach containing dark brown, semifluid material (in one male) and uterus lumen filled with clear fluid (in one female). No abnormalities were noted at other dose levels.
- Necropsy of the dead animals revealed brown stained perineum.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 for arsenic acid is in the range of 50-200 mg/kg bw in mice therefore it is classified as ‘T; R25 Toxic if swallowed’ according to the Annex VI of the Directive 67/548/EEC and ‘category 3’ according to the CLP Regulation (EC) No. 1272/2008.
Executive summary:

In an acute oral toxicity study performed similarly to OECD guideline 401 and in compliance with GLP, groups of Crl:CD-1 (ICR) BR mice (5/sex/dose) were given a single oral dose of arsenic acid (75% w/w) at 75, 100 or 200 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all macroscopically necropsied after death or sacrifice. A preliminary range-finding test was also conducted on 1 mice/sex/dose at four dose levels.

 

Mortalities were 0, 20 and 70% at 75, 100 and 200 mg/kg bw, respectively. All animals showed expected gain in bodyweight over the study period. Clinical signs noted were diarrhoea, hypoactivity, ataxia and tremors which resolved completely by Day 4 in surviving animals. Necropsy of the surviving animals at 75 mg/kg bw revealed stomach containing dark brown, semifluid material (in one male) and uterus lumen filled with clear fluid (in one female). Necropsy of the dead animals revealed brown stained perineum.

Oral LD50 Combined = 149.6 mg/kg bw (114.4 - 195.5)

Oral LD50 Males = 141.4 mg/kg bw (98.8-202.3)

Oral LD50 Females =160.4 mg kg bw(107.1-240.3)

 

The oral LD50 for arsenic acid (75% w/w) is in the range of 50-200 mg/kg bw in mice therefore it is classified as ‘T; R25 Toxic if swallowed’ according to the Annex VI of the Directive 67/548/EEC and ‘category 3’ according to the CLP Regulation (EC) No. 1272/2008.

This study is acceptable and satisfies the guideline requirement for an acute oral study (OECD 401) in mice.