Propionamide

Endpoint summary

Description of key information

In a study according to OECD guideline 423, a LD50 higher than 2000 mg/kg bw was determined for the test item after single oral administration in female rats (reference 7.2.1-1).

In a study according to OECD guideline 402, the acute dermal LD50 of the test item was determined to be greater than 2000 mg/kg bw in rats (reference 7.2.3-1).

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:

2019-03-12 to 2019-04-09

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)

Version / remarks:

December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH, Sulzfeld, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: The mean initial body weight at the start of study was 166 g (range from 158 to 171 g).
- Fasting period before study: Diet was withheld from about 17 to 20 hours before start of treatment until 4 hours after administration.
- Housing: During the acclimation phase, the three rats per treatment group were group-housed in type IV Makrolon® cages with a shelter on softwood bedding material (ABEDD LTE E-001, ABEDD LAB&VET Service GmbH, Austria). Play tunnels (Ref. 14153, Plexx BV, Netherlands) were placed in the cages as additional enrichment. One day before treatment, the rats were single-housed in type III Makrolon" cages with a shelter and a play tunnel on softwood bedding material. Wire grids were placed above the softwood granules. They were removed 4 hours after administration. The rats were kept individually until the end of the observation period. The bedding was changed once a week.
- Diet: ad libitum (VI534, ssniff Spezialdiaten GmbH, Germany)
- Water: ad libitum (drinking water from community water supply)
- Acclimation period: Before start of treatment, the animals were acclimated for at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.7 - 23.6
- Humidity (%): 41.6 - 47.7

Route of administration:

oral: gavage

Vehicle:

other: 0.25% aqueous hydroxypropylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 g/L

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test item preparation was made directly before administration. Appropriate amounts of the test item were suspended in the vehicle using a spatula, a mini shaker (Vortex Genie 2®, Scientific Industries Inc, New York, USA), Ultra-Turrax device (Ultra-Turrax T25, IKA®-Werke GmbH & Co. KG, Staufen, Germany) and a magnetic stirrer. The test item preparation was administered within less than 1 hour after preparation. The stability of the test item in the vehicle was not investigated.

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the chemical properties of the test item, mortality was not expected at the highest starting dose of 2000 mg/kg. Therefore, the treatment was started with 2000 mg/kg in three female rats and continued with further three females at 2000 mg/kg.

Doses:

2000 mg/kg bw/day

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: All animals were weighed before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15.
- Mortality and Clinical Signs: On the day of treatment, each animal was observed for mortality and for symptoms of intoxication at scheduled intervals according to the record sheets. On the following days, the rats were examined once daily. Symptoms were recorded individually for each animal.
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was seen.

Clinical signs:

other: No clinical signs of toxicity were observed.

Gross pathology:

No organ alterations were identified during the gross pathological examination.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.

Executive summary:

An acute oral toxicity study with the test item was performed according to the Acute-Toxic-Class Method and OECD Guideline 423. The treatment was started with 2000 mg/kg body weight in 3 female rats and continued with further 3 females treated with 2000 mg/kg. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. In conclusion, the test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The quality of the experimental study is sufficient as it was conducted according to guideline and under GLP.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-02-28 to 2021-03-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

09 Oct, 2017

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 – 13 weeks
- Weight at study initiation: 204 – 216 g
- Fasting period before study: no
- Housing: The animals were kept in groups except during exposure and unless there were reasons to house individually (e.g. if there is concern that contact with other animals could increase stress due to the nature and severity of the signs of toxicity, or could result in exacerbation of local skin effects) in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding.
- Diet: ad libitum, Altromin 1324 maintenance diet for rats and mice
- Water: ad libitum, tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: at least 5 days
- Microbiological status when known: The animals were derived from a controlled full-barrier maintained breeding system (SPF).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

aqua ad injectionem (sterile water)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10 % of the total body surface
- Type of wrap if used: semi-occlusive dressing made of a porous gauze and non-irritating tape and was fixed with an additional dressing

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was removed using aqua ad injectionem.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: animal 1: 0.43 g, 2: 0.44 g, 3: 0.418 g in 1 mL vehicle
- Constant volume or concentration used: no, but dose and vehicle volume were constant
- For solids, paste formed: no

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on day 1 (prior to the application), on days 8 and 15. A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 6 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis performed.

Preliminary study:

One animal was dosed at a dosage of 2000 mg/kg body weight. As the animal survived, this dose was used as a starting dose for the main study.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr. (total fraction)

Mortality:

No mortality was observed.

Clinical signs:

other: No signs of acute dermal toxicity were observed.

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Other findings:

- Other observations: Slight signs of dermal irritation after a single dose application were observed.
The findings in animal no. 1 were erythema grade 1 (Ø 0.5 cm) on days 8 and 9 and scratches (Ø 1 mm) on days 4, 5 and 10. In animal no. 2 scratches (Ø 1 mm) were observed on days 3, 4, 11 and 12 and in animal no. 3 on days 3-6.
All effects were fully reversible within the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of the test item was determined to be greater than 2000 mg/kg bw in rats.

Executive summary:

An acute dermal toxicity study with the test item was conducted according to OECD TG 402. The study was performed as a fixed dose procedure using female rats. Aqua ad injectionem was used for moistening of the test item for application under semi occlusive conditions for 24 h. At the end of the exposure period the residual test item was removed using aqua ad injectionem and the animals were observed for 14 days after dosing. For the dose range finder one animal was dosed at a dosage of 2000 mg/kg body weight. As the animal survived, this dose was used as a starting dose for the main study. The dose was administered to two animals sequentially. As both animals survived at 2000 mg/kg body weight without showing any signs of systemic toxicity, no further dose was tested. The test item showed no mortality and no signs of acute dermal toxicity, but slight signs of dermal irritation after a single dose application. No oedema was observed in all animals within the observation period. Erythema grade 1 (Ø 0.5 cm) was observed in animal no. 1. Moreover, scratches (Ø 1 mm) were observed in all animals. All effects were fully reversible within the observation period. The body weight development of all female animals was within the expected range. No specific gross pathological changes were recorded for any animal. The LD50 of the test item was determined to be greater than 2000 mg/kg bw. According to OECD guideline 402 the test item has no obligatory labelling requirement for percutaneous toxicity and is not classified. The Acute Toxicity Estimate according to GHS (Globally Harmonized Classification System), 2017 was determined to be 2000 < ATE ≤ 5000 mg test item/ kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The quality of the experimental study is sufficient as it was conducted according to guideline and under GLP.

Additional information

Oral

An acute oral toxicity study with the test item was performed according to the Acute-Toxic-Class Method and OECD Guideline 423. The treatment was started with 2000 mg/kg body weight in 3 female rats and continued with further 3 females treated with 2000 mg/kg. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. In conclusion, the test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.

 

Dermal

An acute dermal toxicity study with the test item was conducted according to OECD TG 402. The study was performed as a fixed dose procedure using female rats. Aqua ad injectionem was used for moistening of the test item for application under semi occlusive conditions for 24 h. At the end of the exposure period the residual test item was removed using aqua ad injectionem and the animals were observed for 14 days after dosing. For the dose range finder one animal was dosed at a dosage of 2000 mg/kg body weight. As the animal survived, this dose was used as a starting dose for the main study. The dose was administered to two animals sequentially. As both animals survived at 2000 mg/kg body weight without showing any signs of systemic toxicity, no further dose was tested. The test item showed no mortality and no signs of acute dermal toxicity, but slight signs of dermal irritation after a single dose application. No oedema was observed in all animals within the observation period. Erythema grade 1 (Ø 0.5 cm) was observed in animal no. 1. Moreover, scratches (Ø 1 mm) were observed in all animals. All effects were fully reversible within the observation period. The body weight development of all female animals was within the expected range. No specific gross pathological changes were recorded for any animal. The LD50 of the test item was determined to be greater than 2000 mg/kg bw. According to OECD guideline 402 the test item has no obligatory labelling requirement for percutaneous toxicity and is not classified. The Acute Toxicity Estimate according to GHS (Globally Harmonized Classification System), 2017 was determined to be 2000 < ATE ≤ 5000 mg test item/ kg body weight.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute oral and dermal toxicity, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.