3-methyl-1,1-diphenylurea

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03.02.-20.02.2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-1,1-diphenylurea

EC Number:

236-039-7

EC Name:

3-methyl-1,1-diphenylurea

Cas Number:

13114-72-2

Molecular formula:

C14H14N2O

IUPAC Name:

3-methyl-1,1-diphenylurea

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material: 3-Methyl-1,1-diphenylurea- Physical state: white solid powder- Composition of test material, percentage of components: main component: 3-Methyl-1,1-diphenylurea CAS:13114-72-2 >98% (w/w) impurities: unlisted additives: unlisted-Molecular formula: C14H14N2O-Molecular weight: 226,27-Batch No.: 14015- Expiration date of the lot/batch: 11/2019- Stability under test conditions: stable- Storage condition of test material: in closed container, in dry room at room temperature (at laboratory conditions)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: breeding farm VELAZ s.r.o., Únětice, Czech Republic, RČH CZ 21760152- Fasting period before study: no- Housing:animal room with monitoring conditions – 1 animals of one sex in one plastic breeding cage- Diet: complete pelleted standard diet for experimental animals, ad libitum- Water: drinking water, ad libitum- Acclimation period: 7 days- Identification of animals: colour marks 1 - 5 on tail of animals, each cage was marked with the number of study, sex and dose of the test substance- Health condition: certificate of good health condition – from breeding farm; no signs of diseases were observed at clinical check-in, during the acclimatisation period and before the start of study.ENVIRONMENTAL CONDITIONS- Temperature (°C): 22 ± 3°C, permanently monitored- Humidity (%): 30 – 70 %, permanently monitored- Photoperiod (hrs dark / hrs light): light period 12-hour light/12 hour dark TIME SCHEDULE OF OBSERVATION Body weight:before application (0th), 8th and 15th day of study Mortality:dailyClinical signs:dailyPathological examination:15th day of study

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE- Area of exposure: 6x6 cm on the back of animals- % coverage: 10% of body surface- Type of wrap if used: mull and held by plaster REMOVAL OF TEST SUBSTANCE- Washing: wiped off with water- Time after start of exposure: after 24 hoursTEST MATERIAL- The test substance in delivered form was applied on the depilated area of skin.

Duration of exposure:

24h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 females/2000 mg/kg5 males/2000 mg/kg

Control animals:

no

Details on study design:

COURSE STUDYThe study was performed as limit test: two groups of animals – 5 males and 5 females at the dose of 2000 mg/kg. The pre-test was performed with 1 male and 1 female of those groups of the five animals. The pre-test was started one day before the start of limit testCLINICAL OBSERVATION-changes in skin and fur, eyes, visible mucous membranes, behaviour of animals, somatomotor activity, reactions to stimuli, and presence of lacrimation, salivation and discharge from nostrils, function of respiratory, digestive and urogenital system-the first day: twice (30 minutes and 3 hours after application)-the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days.PATHOLOGICAL EXAMINATION-Nutritional state, body surface, body foramina, thoracic, abdominal and cranial cavity-sacrificed on the 15th day

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no death of animals

Clinical signs:

No clinical signs of intoxication

Body weight:

In males and females, the weight increments were adequate to species and age of animals in the experiment (see table No.1 and No.2).

Gross pathology:

No macroscopic changes

Any other information on results incl. tables

Table No. 1: Individual body weight of animals – 2000 mg/kg – males

Animal No.	Before application (0th day)	8th day	15th day	Body weight gain (g)
				day 0-8 p.a.	day 8-15 p.a.
1 (pre-test)	231.80	279.90	313.8	48.10	33.90
2	237.30	269.90	304.8	32.60	34.90
3	254.80	293.20	338.6	38.40	45.40
4	244.90	275.60	312.5	30.70	36.90
5	248.70	284.50	313.9	35.80	29.40
Average	243.5	280.62	316.72	37.12	36.1

Table No. 2: Individual body weight of animals – 2000 mg/kg – females

Animal No.	Before application (0th day)	8th day	15th day	Body weight gain (g)
				day 0-8 p.a.	day 8-15 p.a.
1 (pre-test)	211.50	225.50	254.2	14.00	28.70
2	207.20	219.70	228.8	12.5	9.10
3	207.80	210.60	228.2	2.80	17.60
4	216.90	222.10	238.6	5.20	16.50
5	208.60	214.60	240.0	6.00	25.40
Average	210.4	218.5	237.96	8.1	19.46

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance toxicity was evaluated on the basis of mortality, body weight changes, and clinical signs of toxicity during the observation period and necropsy findings at the end of study. The test substance applied on skin at a dose of 2000 mg/kg of animal weight did not cause death of animals. No clinical signs of toxicity were observed during the whole study.No macroscopic changes were diagnosed during pathological examination of all animals. According to the results of study, the value of LD50 (dermal) of the test substance, Akardit, for rats of both sexes is higher than 2000 mg/kg of body weight.

Executive summary:

The test substance,Akardit, was tested for acute dermal toxicity using Wistar rats.

Testing was performed according to Method B.3 - Acute toxicity(Dermal), Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008.

 

The study was performed as limit test: two groups of animals – 5 males and 5 females at the dose of 2000 mg/kg of body weight. The pre-test was performed with 1 male and 1 female from each group. After end exposure test substance of these pilot animals, the other animals of the group were dosed.

The test substance in delivered form was applied on the shaved skin of the test animals for 24 hours.

The test animals were observed 14 days after exposure to test substance, afterwards they were sacrificed, and the necropsy for macroscopic examination of the organs was performed.

    

The test substance applied at the dose of 2000 mg/kg of body weight did not cause death of animals. No clinical signs of toxicity were observed during the whole study. No macroscopic changes were diagnosed during pathological examination.   

 

According to the results of study, the value of LD₅₀(dermal) of the test substance,
Akardit, for rats of both sexes is higher than 2000 mg/kg of body weight.