2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, reaction products with phosphorus oxide

Endpoint summary

Description of key information

 The oral LD50 of the test substance was determined to be ≥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:

experimental study

Adequacy of study:

key study

Study period:

From March 18, 2004 to April 29, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

Specific details on test material used for the study:

- Name of test material (as cited in study report): PARAD substance 139.
- Molecular formula: C6H10O3.xH3O4P.
- Molecular weight: ~250.
- Appearance: Slightly yellowish viscous liquid.
- Analytical purity: n.a. (mixture).
- Density: 1.4488.
- Batch No.: 31104251.
- Expiration date: December 31, 2004.

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).

Key result

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:

other: 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 betwee

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:

other: CLP criteria not met

Remarks:

does not have to be classified

Conclusions:

Under the study conditions, the oral LD50 of the test substance was determined to be ≥2,000 mg/kg bw

Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance 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 test 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

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

A study was conducted to assess the acute oral toxicity of the test substance 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 group of females were dosed at 300, 2000, and 2000 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 2000 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 2000 mg/kg at step 4 was found dead. Macroscopic examination of animal that was found dead revealed abnormalities in the stomach (haemorrhage of glandular mucosa). No abnormalities were found in other animals at termination. Based on the study results, LD50 of the test substance was ≥2,000 mg/kg bw (van Huygevoort AHBM, 2004).

Justification for classification or non-classification

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