N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 2017 to Dec 2017

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: EC No. 440/2008 Part B

Version / remarks:

Acute Toxicity (Dermal), May 2008

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147

Version / remarks:

Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF), November 2000, including the most recent revisions.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

EC Number:

247-361-2

EC Name:

N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

Cas Number:

25952-53-8

Molecular formula:

C8H17N3.ClH

IUPAC Name:

N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide hydrochloride

Test material form:

solid: crystalline

Details on test material:

White crystalline powder

Specific details on test material used for the study:

Batch no: AAN0680
Purity: 99.9%
Expiry: 30 August 2018

Test animals

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

5 males and 5 females per dose group (females will be nulliparous and non-pregnant).
Target age at the initiation of dosing: Between 10 and 12 weeks old. Animals to be used within the study will be of approximately the same age.
Target weight at the initiation of dosing: 230 to 380 g (males) and 130 to 280 (females).
Environmental conditions:
Temperature: 18 to 24°C
Humidity: 40 to 70%
Light Cycle: 12-hours light and 12-hours dark (except during designated procedures)
Ventilation: At least 10 air changes per hour

Administration / exposure

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

A single dose of test item was administered to the appropriate animals by dermal application on Day 1. One day before dosing, an area of approximately 5x7 cm on the back of the animals was clipped. The test item was applied in an area of approximately 10% of the total body surface, i.e. approximately 25 cm² for males and 18 cm² for females. The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only. The application period was 24 hours, after which the dressing was removed and the skin cleaned of residual test item using water.

Duration of exposure:

24 hours

Doses:

The starting dose level was 2000 mg/kg body weight. Based on mortality animals were dosed at the lower doses of 200 and 1000 mg/kg following a stepwise approach. First three females were dosed at 200 mg/kg, based on the absence of mortality in this group three females were dosed at 1000 mg/kg. Finally, two females and five males were dosed at 200 mg/kg in order to achieve guideline requirements. The dose volume for each animal was based on the body weight measurement prior to dosing.A dose volume of 10 mL/kg body weight was used for each dose. The dosing formulations were stirred continuously during dose administration.

No. of animals per sex per dose:

3 females - 200mg/kg
3 females - 1000mg/kg
2 x females, 5 x males - 200mg/kg

Control animals:

no

Details on study design:

A single dose of test item was administered to the appropriate animals by dermal application on Day 1. One day before dosing, an area of approximately 5x7 cm on the back of the animals was clipped. The test item wias applied in an area of approximately 10% of the total body surface, i.e. approximately 25 cm² for males and 18 cm² for females. The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally be used for fixation of the bandages in females only. The application period wias 24 hours, after which the dressing was removed and the skin cleaned of residual test item using water or an appropriate vehicle. The dose level was 2000 mg/kg body weight. The dose volume for each animal was based on the body weight measurement prior to dosing. A dose volume of 10 mL/kg body weight was used for each dose. The dosing formulations was stirred continuously during dose administration.

Results and discussion

Preliminary study:

At 2000 mg/kg, all males and four females were found dead on Day 2 prior to the removal of the test item and the remaining female was killed in extremis on Day 2 prior to the removal of the test item.
At 1000 mg/kg, all three females were found dead on Day 3. At 200 mg/kg, no mortality occurred.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - <= 1 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, all males and four females were found dead on Day 2 prior to the removal of the test item and the remaining female was killed in extremis on Day 2 prior to the removal of the test item.
At 1000 mg/kg, all three females were found dead on Day 3. At 200 mg/kg, no mortality occurred.

Clinical signs:

other: At 2000 mg/kg, no clinical signs were noted on the day of dosing. At 1000 mg/kg, lethargy, hunched posture, uncoordinated movements, piloerection, general erythema of the treated skin, alopecia of the left cheek, chromodacryorrhoea of the snout and/or hyp

Gross pathology:

At 2000 mg/kg, isolated reddish foci on the thymus and/or many dark red foci of the ileum were noted. Gelatinous subcutis of the treated skin and/or forelegs were noted for all animals, this finding was most likely caused by to the treatment method. At 1000 mg/kg, several black foci or dark red discoloration of the glandular mucosa of the stomach were noted. Advanced autolysis was noted for all animals, this finding was considered not toxicologically relevant. At 200 mg/kg, a diaphragmatic hernia of the right medial lobe of the liver was noted for one male, this finding is occasionally seen in rats of this age and strain and was therefore considered not related to treatment.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The dermal LD50 value of 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in Wistar rats was established to be within the range of 200-1000 mg/kg body weight.

Based on these results:
• According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments), 1-(3- Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride should be classified as: toxic in contact with skin (Category 3) for acute toxicity by the dermal route.
• According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures, 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride should be classified as Category 3 and should be labeled as H311: Toxic in contact with skin.