1,3-di-o-tolylguanidine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-03-27 to 2001-04-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

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:

1,3-di-o-tolylguanidine

EC Number:

202-577-6

EC Name:

1,3-di-o-tolylguanidine

Cas Number:

97-39-2

Molecular formula:

C15H17N3

IUPAC Name:

1,3-di-o-tolylguanidine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: charles River Laboratories, L'Arbresle, France.
- Age at study initiation: 8 week old (on the day of treatment)
- Weight at study initiation: 241+/-12 g (males), 227+/-9g (females)
- Fasting period before study: no data
- Housing: individually in polycarbonate cages with stainless steel lid (35.5 cm x 23.5 cm x 19.3 cm).
- Diet (e.g. ad libitum): free access to A04 C pelleted diet (UAR Villoisson, france)
- Water (e.g. ad libitum): filtered water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2°C
- Humidity (%):30 to 70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
On the day before treatment, the dorsal area of each animal was clipped (area = 6 cm x 8 cm) using an electric clipper. Only animals with healthy intact skin were used for the study.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
On removal of the dressing, any residual test substance was removed using a moistened cotton pad.

TEST MATERIAL
A single dose of 2000 mg/kg of DOTG in its original form was placed on a hydrophylic gauze pad pre-moistened with 2 mL of water and then applied to an area of the skin representing approximately 10 % of the total body surface of the animals.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Observations and weighing: The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. The animals were weighed individually just before administration of DOTG on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs and no cutaneous reactions were observed during the study. A slight white coloration of the skin was noted in all animals on days 2 and 3.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Other findings:

no

Any other information on results incl. tables

Table 1: Individual and mean body weight and weekly body weight change (g)

 

Dose mg/kg	sex	animals	Days
			1	1-8	8	8-15	15
2000	male	01	262	49	311	50	361
		02	243	47	290	48	338
		03	233	53	286	44	330
		04	236	49	285	52	337
		05	232	33	265	33	298
		M	241	46	287	45	333
		SD	12	8	16	8	23
2000	female	06	232	25	257	17	274
		07	226	12	238	3	241
		08	219	7	226	7	233
		09	218	25	243	17	260
		10	238	6	244	14	258
		M	227	15	242	12	253
		SD	9	9	11	6	16

 

1-8: body weight gain between D1 and D8

8-15: body weight gain between D8 and D15

M: mean

SD: standard deviation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under these experimental conditions, the dermal LD0 of the test substance DOTG is equal to or higher than 2000 mg/kg in rats, because no signs of toxicity were observed at this dose.

Executive summary:

The test substance was applied in its original form at the dose of 2000 mg/kg to the skin of one group of ten rats (5 males and 5 females). The test site was covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test substance. All animals were subjected to necropsy.

No clinical signs and no deaths were observed during the study. The body weight gain of the animals was similar to that of historical control animals. A slight white coloration of the skin was noted in all animals on days 2 and 3. No cutaneous reactions were observed. No apparent abnormalities were observed at necropsy in any animal.

Under these experimental conditions, the dermal LD0 of the test substance DOTG is equal to or higher than 2000 mg/kg in rats.