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Description of key information

 The oral LD50of the read across substance was ≥2,000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From March 18, 2004 to April 29, 2004
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted with read across substance according to OECD Guideline 423, EU Method B.1, EPA OPPTS 870.1100 and JMAFF Japanese test guidelines, 2000, in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Japanese test guidelines
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Test animals
- Supplier: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: 9-12 weeks old.
- Fasting period: Food was withheld overnight (for a maximum of 20 h) prior to dosing and 3-4 h after dosing.
- Acclimatisation period: At least 5 d.
- Water: Free access to tap-water.
- Diet: Free access to standard pelleted laboratory animal diet.

Animal husbandry
- Animals per cage: 3 animals.
- Housing: Macrolon cages (type IV; height 18 cm) containing purified sawdust as bedding material.
- Diet supplier: Altromin (code VRF 1), Lage, Germany.

Environmental conditions
- Air changes: Approximately 15 air changes per h.
- Temperature: 21±3°C.
- Humidity: 30 - 70%.
- Photoperiod: 12 h artificial fluorescent light and 12 h darkness per d.
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
Dosing method: Oral gavage, using a stainless steel stomach tube
Dose preparation: The formulations (w/w) were prepared in vehicle (propylene glycol) 4 h prior to dosing.
Doses:
300, 2,000 mg/kg
No. of animals per sex per dose:
3 females
Control animals:
not specified
Details on study design:
- Dosing: Initially, the test substance was administered by oral gavage to three female Wistar rats at 300 mg/kg bw. Further, in a stepwise procedure additional groups of females were dosed at 300, 2,000, and 2,000 mg/kg bw.
- Dose volume: 10 mL/kg

Frequency of observations:
- Mortality/viability- Twice daily
- Body weight: Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored
- Necropsy: Animals were sacrificed by asphyxiation using a oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
1 animal died at dose level of 2,000 mg/kg bw administered at step 4.
Clinical signs:
At 300 mg/kg- Hunched posture and uncoordinated movements.
At 2,000 mg/kg- Hunched posture, uncoordinated movements, lethargy, chromodacryorrhoea (snout), piloerection, flat gait and salivation.
The surviving animals had recovered from the symptoms between Day 1 and 4.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Macroscopic post mortem examination of the animal that was found dead during the study revealed abnormalities in the stomach (hemorrhage of glandular mucosa).

Macroscopic post mortem examination of the other animals at termination did not reveal any abnormalities.

Table 1: Incidence of mortality

Dose level

Mortality

300 mg/kg

0/3

300 mg/kg

0/3

2,000 mg/kg

0/3

2,000 mg/kg

1/3

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of the substance was ≥2,000 mg/kg bw
Executive summary:

A study was conducted to assess the acute oral toxicity of the read across substance (2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, reaction products with phosphorus oxide (P2O5)) in female rats according to OECD Guideline 423, EU Method B.1 and EPA OPPTS 870.1100, in compliance with GLP. Initially, the test substance was administered by oral gavage to three female Wistar rats at 300 mg/kg bw. Further, in a stepwise procedure additional groups of females were dosed at 300, 2,000, and 2,000 mg/kg bw. Treated animals were then observed for mortality, clinical signs and body weight changes for 14 d and were then culled and subjected to gross pathological examination. In the rats treated at 300 mg/kg bw, clinical signs such as hunched posture and uncoordinated movements were observed. The rats treated at 2,000 mg/kg bw, revealed clinical signs that included hunched posture, uncoordinated movements, lethargy, chromodacryorrhoea (snout), piloerection, flat gait and salivation. Surviving rats had recovered from the symptoms between Day 1 and 4. The mean body weight gain in the treated rats was normal. One animal of the dose level 2,000 mg/kg at step 4 was found dead. Macroscopic examination of animal that was found dead revealed abnormalities in the stomach (hemorrhage of glandular mucosa). No abnormalities were found in other animals at termination. Based on the study results, LD50 of the read acropss substance was ≥2,000 mg/kg bw (van Huygevoort AHBM, 2004).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
High quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

A study was conducted to assess the acute oral toxicity of the read across substance (2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, reaction products with phosphorus oxide (P2O5)) in female rats according to OECD Guideline 423, EU Method B.1 and EPA OPPTS 870.1100, in compliance with GLP. Initially, the test substance was administered by oral gavage to three female Wistar rats at 300 mg/kg bw. Further, in a stepwise procedure additional groups of females were dosed at 300, 2,000, and 2,000 mg/kg bw.Treated animals were then observed for mortality, clinical signs and body weight changes for 14 d and were then culled and subjected to gross pathological examination. In the rats treated at 300 mg/kg bw, clinical signs such as hunched posture and uncoordinated movements were observed. The rats treated at 2,000 mg/kg bw, revealed clinical signs that included hunched posture, uncoordinated movements, lethargy, chromodacryorrhoea (snout), piloerection, flat gait and salivation. Surviving rats had recovered from the symptoms between Day 1 and 4.The mean body weight gain in the treated rats was normal. One animal of the dose level 2,000 mg/kg at step 4 was found dead. Macroscopic examination of animal that was found dead revealed abnormalities in the stomach (hemorrhage of glandular mucosa). No abnormalities were found in other animals at termination. Based on the study results, LD50 of the read acropss substance was ≥2,000 mg/kg bw (van Huygevoort AHBM, 2004).


Justification for selection of acute toxicity – oral endpoint
The study was conducted according to internationally accepted guidelines, in compliance with GLP.

Justification for classification or non-classification

Acute oral toxicity:

Based on the results of an acute oral toxicity study with read across substance, the test substance does not need to be classified for this endpoint according to the EU CLP criteria (EC 1272/2008).

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