Methyl 2,3-dibromopropionate

Endpoint summary

Description of key information

Acute oral toxicity:

LD50: 300-2000 mg/kg bw (actual value 500 mg/kg bw) (OECD Guideline 423)

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 2019-01-03 to 2019-02-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study performed to current OECD guidelines with no significant deviations and run in OECD GLP certified lab.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Purity: 98%
Batch No.: 800327680

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approximately 10-12 weeks old)
- Weight at study initiation: 140.0 to 178.0 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Housing: On arrival and following assignment to the study, animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilized sawdust as bedding material equipped with water bottles.
- Diet: Pelleted rodent diet was provided ad libitum
- Water: Municipal tap-water was freely available to each animal via water bottles.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 21 °C (actual daily mean temperature)
- Humidity (%): actual daily mean relative humidity of 36 to 53%
- Air changes (per hr): Ten or greater
- Photoperiod (hrs dark / hrs light): A 12 hour light/12 hour dark cycle

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

CLASS METHOD
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

300 and 2000 mg/kg body weight

No. of animals per sex per dose:

three female rats for each treatment group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing
General health/mortality and moribundity: twice daily
Clinical Observations: Postdose observations: on the day of dosing (at least three times) and once daily thereafter
Body Weights: on Day 1 (predose), 8 and 15
- Necropsy of survivors performed: yes, sacrificed by oxygen/carbon dioxide procedure

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

At 300 mg/kg, two females were found dead on Day 2 post-treatment one at each dose group). No further mortality occurred at 300 mg/kg. At 2000 mg/kg, all animals were found dead on Day 1 post-treatment.

Clinical signs:

other: At 300 mg/kg, hunched posture, pale appearance, piloerection and salivation were noted for the animals between Days 1 and 12. At 2000 mg/kg, lethargy, ventro-lateral recumbency, flat and hunched posture, uncoordinated movements, pale appearance, piloerect

Gross pathology:

At 2000 mg/kg, abnormalities of the stomach (glandular mucosa, many reddish foci) were found in the two of the animals that died on Day 1. Macroscopic post mortem examination of the remaining animals of the study did not reveal any abnormalities.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 value of the test item in Wistar Han rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.

Executive summary:

The study was carried out in compliance with OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

Initially, the test item was administered by oral gavage to three female Wistar Han rats at 300 mg/kg body weight. In a stepwise procedure two additional groups of three females were dosed at 300 and 2000 mg/kg body weight. The animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

 

At 300 mg/kg, two females were found dead on Day 2 post-treatment (one at each dose group). No further mortality occurred at 300 mg/kg. At 2000 mg/kg, all animals were found dead on Day 1 post-treatment.

At 300 mg/kg, hunched posture, pale appearance, piloerection and salivation were noted for the animals between Days 1 and 12.At 2000 mg/kg, lethargy, ventro-lateral recumbency, flat and hunched posture, uncoordinated movements, pale appearance, piloerection, watery discharge from both eyes and salivation were noted for the animals prior to death (on Day 1).

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

At 2000 mg/kg, abnormalities of the stomach (glandular mucosa, many reddish foci) were found in the two of the animals that died on Day 1. Macroscopic post mortem examination of the remaining animals of the study did not reveal any abnormalities.

 

The oral LD50 value of the test item in Wistar Han rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Quality of whole database:

Study performed to current OECD guidelines with no significant deviations and run in OECD GLP certified lab.

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:

The study was carried out in compliance with OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

Initially, the test item was administered by oral gavage to three female Wistar Han rats at 300 mg/kg body weight. In a stepwise procedure two additional groups of three females were dosed at 300 and 2000 mg/kg body weight. The animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

 

At 300 mg/kg, two females were found dead on Day 2 post-treatment (one at each dose group). No further mortality occurred at 300 mg/kg. At 2000 mg/kg, all animals were found dead on Day 1 post-treatment.

At 300 mg/kg, hunched posture, pale appearance, piloerection and salivation were noted for the animals between Days 1 and 12.At 2000 mg/kg, lethargy, ventro-lateral recumbency, flat and hunched posture, uncoordinated movements, pale appearance, piloerection, watery discharge from both eyes and salivation were noted for the animals prior to death (on Day 1).

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

At 2000 mg/kg, abnormalities of the stomach (glandular mucosa, many reddish foci) were found in the two of the animals that died on Day 1. Macroscopic post mortem examination of the remaining animals of the study did not reveal any abnormalities.

 

The oral LD50 value of the test item in Wistar Han rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.

Justification for classification or non-classification

Acute oral LD50: 300-2000 mg/kg bw (actual value 500 mg/kg bw).

Therefore in accordance with Regulation (EC) No. 1272/2008 (amendment 286/2011) Table 3.1.1, this substance should be classified as Category 4 for this endpoint.

 

Specific target organ toxicity-single exposure:

No significant non-lethal toxic effects observed in acute oral toxicity study.

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.8.1, this substance should not be classified for this endpoint.