2-benzyl-2-dimethylamino-4'-morpholinobutyrophenone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-07-26, 1988-09-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-benzyl-2-dimethylamino-4'-morpholinobutyrophenone

EC Number:

404-360-3

EC Name:

2-benzyl-2-dimethylamino-4'-morpholinobutyrophenone

Cas Number:

119313-12-1

Molecular formula:

C23 H30 N2 O2

IUPAC Name:

2-benzyl-2-(dimethylamino)-1-[4-(morpholin-4-yl)phenyl]butan-1-one

Details on test material:

- Substance type: Organic
- Physical state: Solid
- Analytical purity: Lab. sample
- Lot/batch No.: Z 1436/37R
- Expiration date of the lot/batch: 1991-06
- Storage condition of test material: Room temperature, in the dark
- Other: Insoluble in water

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain as stated in the report: Tif: RAI f (SPF)
- Source: CIBA-GEIGY Ltd., Animal Production, Stein / Switzerland
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 224 - 259
- Housing: Individually in Macrolon cages type 3, with standardized soft wood bedding (Société Parisienne des Sciures, Pantin)
- Diet: Ad libitum, NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland, Rat chow
- Water: Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): appr. 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

peanut oil

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- % coverage: 10 %
- Type of wrap if used: gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With lukewarm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg body weight
- Constant volume or concentration used: yes
- For solids, paste formed: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 males and 5 females. Six male rats have been used, since a male rat was mistakenly applied in the female group. The treatment was repeated with the missing fifth female.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality, signs and symptoms daily; body weight at start, on day 7, and on day 14
- Necropsy of survivors performed: yes

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Piloerection, abnormal body positions, and dyspnea were seen, being common symptoms in acute dermal tests. The animals recovered within 7 to 9 days. See Table 1.

Gross pathology:

No deviations from normal morphology

Other findings:

None

Any other information on results incl. tables

Table 1. Observation of symptoms*

Observations	Appl. day	Days after application
		1	2	3	4	5	6	7	8	9	>9
2000 mg/kg, males
piloerection	+	+	+	+	+	+	+	+	+
hunched posture		+	+	+	+
ventr.recumbency	+	+
dyspnea	+	+	+	+	+
2000 mg/kg, females
piloerection	+	+	+	+	+	+	+	+	+
hunched posture		+	+	+	+
ventr.recumbency	+	+
dyspnea		+	+	+	+

* + = slight; ++ = moderate; +++ = severe

Table 2. Mean body weight and standard deviation

Group	Appl.day	Day 7	Day 14
Males	242 ± 3.2	272 ± 7.7	302 ± 16.1
Females	245 ± 13.9	260 ± 18.6	269 ±30.2

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity LD50 to rats was determined to be >2000 mg/kg bw under the conditions of the test.

Executive summary:

In this guideline (OECD 402) study conducted to GLP standards, the test material (EC 404-360-3) was determined to be practically nontoxic, with an acute dermal LD50 > 2000 mg/kg bw. The test was conducted on rats (male/female) using a single dose of 2000 mg/kg bw and the test material was applied using a vehicle of peanut oil and held in place using a semiocclusive cover. As no mortalities occured the test material is not classified as acutely toxic (dermal) under CLP regulation 1272/2008.