Propionamide

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

Propionamide

EC Number:

201-172-1

EC Name:

Propionamide

Cas Number:

79-05-0

Molecular formula:

C3H7NO

IUPAC Name:

propanamide

Test material form:

solid

Test animals

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

Administration / exposure

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.

Results and discussion

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.

Effect levels

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.

Applicant's summary and conclusion

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.