Propanoic acid, 2-[(ethoxythioxomethyl)thio]-, methyl ester

Endpoint summary

Description of key information

Acute toxicity, oral, rat male/female LD50 = between 500 and 2000 mg/kg (TNO, 2000)

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:

2000

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:

yes

Remarks:

The 2000 mg/kg dose level was examined in both sexes, although mortality was observed in the first sex treated. This was due to an interval too short to detect mortality after dosing of the first sex. This deviation has no impact on the study.

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

see above

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Wistar outbred; Crl:(WI)WU BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Source: Charles River, Germany
- Age at study initiation: 5-6 weeks old upon arrival
- Weight at study initiation: no data available
- Fasting period before study: Prior to dosing, the animals had fasted overnight.
- Housing: a maximum of five animals per stainless steel cage
- Food consumption: standard laboratory rodent diet ad libitum. Each batch of this diet is analyzed by the supplier (SDS Special diets services, Whitham, England).
- Water consumption: Tap water (N.V. Waterleidingbedrijf Midden-Nederland) ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are available upon request.
- Acclimation period: 6 to 9 days

ENVIRONMENTAL CONDITIONS :
- Temperature: 22 ± 3°C
- Humidity: 30 to 70%
- Air changes: ca 10 air changes/hour
- Photoperiod: 12 h dark/12 h light

In-life dates: From: 17-MAY-2000 To: 22-JUNE-2000

Route of administration:

oral: gavage

Vehicle:

maize oil

Remarks:

for the concentration 500 mg/lg

Details on oral exposure:

* Vehicle:
- Concentration in vehicle: 500 mg/kg
- Amount of vehicle : 1 mL/kg
- Justification for choice of vehicle: data not available
- Lot/batch no. : data not available
- Purity: data not available

* Maximum dose volume applied: 1 ml/kg body weight of a 500 mg/ml dilution of the test substance in maize oil or 1.74 ml/kg body weight of the undiluted test substance (density 1.15 kg/l)
* Dosage preparation: The exact amount of the test substance to be dosed was calculated for each anamal individually.
* Class method:
- Rationale for the selection of the starting dose: according to the information provided by the Sponsor

Doses:

500 and 2000 mg/kg/bw

No. of animals per sex per dose:

2 x 3 females + 2 x 3 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical signs and mortality: Observations were made within 1 hour and within 4 hours after dosing, and subsequently in surviving animals at least once daily throughout an observation period of 14 days.
> Body weight: The body weight of each animal was recorded immediately before dosing on day 0, and of the surviving animals on days 3, 7 and 14 of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: none

Statistics:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 500 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

1/3 male died at 500 mg/kg and all animals (male/female) died at 2000 mg/kg
Male: 500 mg/kg bw; Number of animals: 3; Number of deaths: 1
Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 3
Female: 500 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 3

Clinical signs:

other: At 500 mg/kg, sluggishness, blepharospam, salivation, lacrimation and, piloerection were observed. At 2000 mk/kg, sluggishness, hunching and, lacrimation were observed.

Gross pathology:

Examination at autopsy of the males and females or of animals that had died did not reveal distinct treatment-related gross alterations.

Other findings:

none

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the experimental conditions of this study, the oral LD50 of the test item Rhodixan A-1 was between 500 and 2000 mg/kg in rats.

Executive summary:

RHODIXAN A-1 was tested for acute oral toxicity in Wistar rats, according to O.E.C.D. guideline N° 423/EEC method B.1ter, and in compliance with Good Laboratory Practice.

The test article, (a liquid, specific gravity: 1.15) was administered by gavage at 500 mg/kg (dose volume: 1 ml/kg, in maize oil) and 2000 mg/kg (dose volume: 1.74 ml/kg, undiluted) to groups of 3 males and 3 females. Examinations for mortality, clinical signs and body weight gain were performed during a 14-day observation period. All surviving animals were euthanatized and necropsied at the end of the observation period.

 

One male was found dead 2 days after treatment with the 500 mg/kg. All animals treated at 2000 mg/kg died within one day after dosing. Clinical signs consisted mainly of sluggishness, blepharospasm, lacrimation and piloerection. Macroscopic examination of all the animals did not reveal any treatment-related gross changes. All surviving animals gained weight during the 14-day study period.

Based on these results, the LD50 was considered to be between 500 mg/kg and 2000 mg/kg, and RHODIXAN A-1 should be classified Acute toxicity, Oral, Category 4 H302: Harmful if swallowed according to GHS criteria.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

GLP study conducted according to OECD guideline no. 423 (Klimish score = 1)

Additional information

Acute oral toxicity:

One klimisch score 1 study was available and was used as a key study:

In this study (2000), RHODIXAN A-1 was tested for acute oral toxicity in Wistar rats, according to O.E.C.D. guideline N° 423/EEC method B.1ter, and in compliance with Good Laboratory Practice. The test article, (a liquid, specific gravity: 1.15) was administered by gavage at 500 mg/kg (dose volume: 1 ml/kg, in maize oil) and 2000 mg/kg (dose volume: 1.74 ml/kg, undiluted) to groups of 3 males and 3 females. Examinations for mortality, clinical signs and body weight gain were performed during a 14-day observation period. All surviving animals were euthanatized and necropsied at the end of the observation period. One male was found dead 2 days after treatment with the 500 mg/kg. All animals treated at 2000 mg/kg died within one day after dosing. Clinical signs consisted mainly of sluggishness, blepharospasm, lacrimation and piloerection. Macroscopic examination of all the animals did not reveal any treatment-related gross changes. All surviving animals gained weight during the 14-day study period. Based on these results, the LD50 was considered to be between 500 mg/kg and 2000 mg/kg.

Justification for classification or non-classification

Harmonized classification:

No harmonized classification is available according to the Regulation (EC) No 1272/2008.

Self-classification:

Rhodixan A-1 is classified for acute oral toxicity as Acute tox. 4, H302 (Harmful if swallowed) according to the Regulation (EC) 1272/2008 (CLP) as the oral LD50 (rat) is between 500 and 2000 mg/kg.