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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study can be compared to the deleted OECD 401 guideline for testing acute oral toxicity. The study was not performed under GLP.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
number of animals and number of doses
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Phosphonic acid
EC Number:
237-066-7
EC Name:
Phosphonic acid
Cas Number:
13598-36-2
Molecular formula:
H3O3P
IUPAC Name:
phosphonic acid
Details on test material:
- Name of test material (as cited in study report): Phosphorous acid
- Physical state: Liquid
- Composition of test material, percentage of components: confidential

Test animals

Species:
rat
Strain:
other: Charles River CD strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 360-440 g (males) and 215-300 g (females)
- Fasting period before study: overnight
- Housing: 3 rats per cage, in suspended plastic cages in a barrier-maintained room
- Diet: Spratts No. 2 autoclaved small animal diet
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): ca. 50%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: de-ionised water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10% w/w

MAXIMUM DOSE VOLUME APPLIED: The dose-volume was varied according to the dose level
Doses:
1360, 1520, 1700, 1910, 2140, 2390, 2680, and 3000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology
Statistics:
The Oral Median Lethal Dose (LD50) and its 95% Confidence Limits were determined using the method of Weil.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1 580 mg/kg bw
95% CL:
>= 1 470 - <= 1 690
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 560 mg/kg bw
95% CL:
>= 1 440 - <= 1 690
Mortality:
At 1360 mg/kg: no mortality occurred.
At 1520 mg/kg: both males and females 4 out of 6 (4/6) died within 2 days after dosing.
At 1700 mg/kg: males 3/6 and females 4/6 died within 3 days after dosing.
At 1910, 2140, and 2390 mg/kg: all 6 males and females 5/6 died within 2-4 days after dosing.
At 2680 and 3000 mg/kg: all animals died within 1 day after dosing.
Clinical signs:
At all dose levels lethargy and piloerection were seen. Red nasal encrustation, loose faeces and ataxia were also seen at dose levels of 1700 mg/kg and above. Brown staining around the mouth was seen at dose levels of 2390 mg/kg and above, while prostration and convulsion were seen only in rats receiving 3000 mg/kg. The time of onset of clinical signs was dose related and varied between 10 minutes after dosing at 3000 mg/kg and 1-17 hours after dosing at the three lower dose levels. All surviving animals had completely recovered by 48 hours after dosing.
Body weight:
No data on body weight changes
Gross pathology:
Animals which died during the study:
- Lung: dark red/pink and firm to the touch.
- Stomach: contents – brown/black fluid. The stomach lining appeared ulcerated at dose levels of 1520 mg/kg and above.
- Intestines: contents - brown/black fluid. The lining appeared hyperaemic.
- Spleen: 3000 mg/kg - darker than normal. All other dose levels – paler than normal.
- Thymus: darker than normal.
- Kidneys: paler than normal.
- Liver: paler than normal.
It was noted that organs had a grey/brown discolouration where they came in contact with the stomach, intestines or liver, which, themselves, were similarly discoloured.
Animals killed at the end of the 14-day observation period:
- Liver, kidneys, and spleen: paler than normal, especially where they were in contact with the gastro-intestinal tract.
- Lungs: deeper pink than normal.
Other findings:
- Other observations: The brown/black fluid observed in the gastro-intestinal tract of animals which died is possibly franked blood and may be indicative of haemorrhage. The effect on the organs surrounding the stomach, as indicated by the grey/brown discolouration, may have been a direct result of the acidity of the compound.

Any other information on results incl. tables

There is no observable difference between the LD50 values obtained in males and females.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information if swallowed Criteria used for interpretation of results: EU
Conclusions:
The oral median lethal dose ( LD50) of 10% Phosphorous acid (w/w) in water was determined in rats. The LD50 and its 95% confidence limits was 1580 (1470-1690) mg/kg for male rats and 1560 (1440-1690) mg/kg for female rats. Based on these results and according to the EU classification criteria outlined in 67/548/EEC and 1272/2008 the compound needs to be classified as harmful if swallowed.
Executive summary:
Male and female albino rats of the Charles River CD strain were treated with 10% Phosphorous acid by oral gavage administration at 1360, 1520, 1700, 1910, 2140, 2390, 2680, and 3000 mg/kg bw. The rats were observed for 14 days following dosing after which surviving animals were sacrificed and examined macroscopically. Mortality and clinical signs were recorded. At 1360 mg/kg: no mortality occurred. At 1520 mg/kg: both males and females 4 out of 6 (4/6) died within 2 days after dosing. At 1700 mg/kg: males 3/6 and females 4/6 died within 3 days after dosing. At 1910, 2140, and 2390 mg/kg: all 6 males and females 5/6 died within 2-4 days after dosing. At 2680 and 3000 mg/kg: all animals died within 1 day after dosing. At all dose levels lethargy and piloerection were seen. Red nasal encrustation, loose faeces and ataxia were also seen at dose levels of 1700 mg/kg and above. Brown staining around the mouth was seen at dose levels of 2390 mg/kg and above, while prostration and convulsion were seen only in rats receiving 3000 mg/kg. The time of onset of clinical signs was dose related and varied between 10 minutes after dosing at 3000 mg/kg and 1-17 hours after dosing at the three lower dose levels. All surviving animals had completely recovered by 48 hours after dosing. The brown/black fluid observed in the gastro-intestinal tract of animals which died is possibly franked blood and may be indicative of haemorrhage. The effect on the organs surrounding the stomach, as indicated by the grey/brown discolouration, may have been a direct result of the acidity of the compound. The Oral Median Lethal Dose (LD50) and its 95% confidence limits were determined using the method of Weil.There was no observable difference between the LD50 values obtained in males and females.The LD50 and its 95% confidence limits was 1580 (1470-1690) mg/kg for male rats and 1560 (1440-1690) mg/kg for female rats. Based on these results and according to the EU classification criteria outlined in 67/548/EEC and 1272/2008 the compound needs to be classified as harmful if swallowed.