2,5-dimethyl-1H-pyrrole

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD Guideline Study but only one animal tested

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 404

Deviations:

no

Principles of method if other than guideline:

The study was performed in a stepwise manner and was started by treatment of a single rabbit
(sentinel). Since mortality occurred in the first animal, the two other animals assigned to the
study were not treated.

GLP compliance:

yes (incl. QA statement)

Test type:

other: OECD 404

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,5-dimethyl-1H-pyrrole

EC Number:

210-913-8

EC Name:

2,5-dimethyl-1H-pyrrole

Cas Number:

625-84-3

Molecular formula:

C6H9N

IUPAC Name:

2,5-dimethyl-1H-pyrrole

Constituent 2

Reference substance name:

2,5-Dimethylpyrrole

IUPAC Name:

2,5-Dimethylpyrrole

Test material form:

other: yellowish liquid

Details on test material:

Purity 99.7%

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

Albino rabbit, New Zealand White, (SPF-Quality).
Recognised by international guidelines as the recommended test
system (e.g. EC, OECD)
Source: Charles River Deutschland, Kisslegg, Germany
1 Male.
The animal used within the study was at least 6 weeks old and
body weight was at least 1.0 kg.
Earmark.
A health inspection was performed prior to the commencement of
treatment, to ensure that the animal was in a good state of health.
Special attention was paid to the skin to be treated, which was
intact and free from abnormalities.
Conditions
The animal was housed in a controlled environment, in which optimal conditions were
considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual
range: 20.3 - 21.2°C), a relative humidity of 30-70% (actual range: 25 - 62%) and 12 hours
artificial fluorescent light and 12 hours darkness per day.
Accommodation
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions
56x44x37.5 cm).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet
Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits,
Altromin, Lage, Germany) approx. 100 g. per day. Hay (TecniLab-BMI BV, Someren, The
Netherlands) was provided at least three times a week.
Water
Free access to tap water.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers,
exposing an area of approximately 150 square centimeters (1 Ox15 cm2
),
The animal was treated by dermal application of 0,5 ml of the test substance. The test
substance was applied to the skin of one flank, using a metalline patch# of 2x3 cm, The patch
was mounted on Micropore tape#, which was wrapped around the abdomen and secured with
Coban elastic bandage#.
Four hours after the application, the dressing was removed and the skin cleaned of residual test
substance using tap water.

Duration of exposure:

After the 20 hours observation, the animal was sacrificed by intra-venous injection of
pentobarbital (Euthesate®; Sanofi Sante BV, Maassluis, The Netherlands) after showing
lethargy and labored respiration.

Doses:

The animal was exposed for four hours to 0.5 ml of 2,5-DIMETHYLPYRROLE.

No. of animals per sex per dose:

1 rabbit (male)

Control animals:

yes, concurrent no treatment

Details on study design:

The animal was exposed for four hours to 0.5 ml of 2,5-DIMETHYLPYRROLE. Approximately 1
hour after exposure, the animal showed lethargy. Immediately after the 20 hours observation,
the animal was sacrificed for humane reasons after showing laboured respiration, a pale
appearance, body weight loss and the animal felt cold. Macroscopic post mortem examination
showed haemorrhages in the lungs.
The other two animals assigned to the study were not treated.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD100

Effect level:

ca. 165 mg/kg bw

Based on:

test mat.

Mortality:

Since mortality occurred after four hours of epidermal exposure to 2,5-DIMETHYLPYRROLE on
the rabbit skin, proper assessment of the skin irritating properties of the substance is not
possible.
The dose applied in terms of mg/kg body weight is equivalent to approximately 165 mg/kg.

Clinical signs:

The animal was exposed for four hours to 0.5 ml of 2,5-DIMETHYLPYRROLE. Approximately 1
hour after exposure, the animal showed lethargy. Immediately after the 20 hours observation,
the animal was sacrificed for humane reasons after showing laboured respiration, a pale
appearance, body weight loss and the animal felt cold.

Body weight:

The animal used within the study was at least 6 weeks old and
body weight was at least 1.0 kg.

Gross pathology:

Macroscopic post mortem examination
showed haemorrhages in the lungs.

Other findings:

Exposure to 2,5-DIMETHYLPYRROLE resulted in well-defined erythema and/or very slight
oedema, between 1 and 20 hours after exposure. There was no evidence of a corrosive effect on the skin.
Yellow staining of the treated skin by the test substance was observed throughout the
observation period.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Toxic in contact with skin (Category 3).
The dose applied in terms of mg/kg body weight is equivalent to approximately 165 mg/kg.

Executive summary:

Primary skin irritation/corrosion study with 2,5-DIMETHYLPYRROLE in the rabbit (4-hour semiocclusive

application).

The study was carried out based on the guidelines described in:

OEeD NoA04, "Acute Dermal Irritation/Corrosion" (2002)

EC, Council Directive 67/548/EEC, AnV, BA (2004), "Acute Toxicity: Dermal Irritation/ Corrosion"

US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation

JMAFF Guidelines (2000) including the most recent partial revisions.

One rabbit was exposed to 0.5 ml of 2,5-DIMETHYLPYRROLE by application onto clipped skin

for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1 and 20 hours after

exposure.

Approximately 1 hour after exposure, the animal showed lethargy. Immediately after the 20

hours observation, the animal was sacrificed for humane reasons after showing laboured

respiration, a pale appearance, body weight loss and the animal felt cold. Macroscopic post

mortem examination showed haemorrhages in the lungs.

The other two animals assigned to the study were not treated.

Skin effects observed were well-defined erythema and/or very slight oedema, between 1 and 20

hours after exposure.

Yellow staining of the treated skin by the test substance was observed throughout the

observation period.

Since mortality occurred after four hours of epidermal exposure to 2,5-DIMETHYLPYRROLE on

the rabbit skin, proper assessment of the skin irritating properties of the substance is not

possible.

The dose applied in terms of mg/kg body weight is equivalent to approximately 165 mg/kg.

The results indicate that the substance might be classified and labelled for toxicity via the

dermal route:

- According to the Globally Harmonized System of Classification and Labeling of Chemicals

(GHS) of the United Nations (New York and Geneva, 2003):

Fatal in contact with skin (Category 2) or Toxic in contact with skin (Category 3).

- EC criteria for classification and labeling requirements for dangerous substances and

preparations (Council Directive 67/548/EEC): Toxic in contact with skin (R24)