Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was undertaken between 1 and 15 September 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): D.I.X.T
- Physical state: Yellow, oily viscous liquid
- Batch No. 20-H-87
- Purity: 90% min (by HPLC)
- Storage condition of test material: ambient temperature in the dark

Test animals

Species:
rat
Strain:
other: CD rats [Crl: COBS CD(SD)BR]
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Obtained from Charles River U.K. Limited, Margate, Kent, England.
- Age at study initiation: Seven to ten weeks of age.
- Weight at study initiation: 200 to 240 g.
- Fasting period before study: None.
- Housing: Rats were housed individually in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): A standard laboratory rodent diet (Labsure LAD 1) was provided ad libitum.
- Water (e.g. ad libitum): Water was provided ad libitum.
- Acclimation period: At least twenty days prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The mean daily minimum and maximum temperatures were 22°C and 25°C.
- Humidity (%): The mean daily relative humidity value was 55%.
- Air changes (per hr): The rate of air exchange was maintained at approximately 15 air changes/hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to give 12 hours artificial light in each 24 hour period.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Remarks:
None
Details on dermal exposure:
TEST SITE
One day prior to treatment hair was removed from the dorso-lumbar region of each rat with electric clippers exposing an area equivalent to 10% of the total body surface.

The test substance was applied by spreading it evenly over the prepared skin. The treated area was then promptly covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk.



REMOVAL OF TEST SUBSTANCE
At the end of the 24-hours exposure period, the dressings were carefully removed and the treated area of skin decontaminated by washing in warm water and blotting dry with absorbent paper.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The rats were treated at 2.0 g/kg bodyweight.


Duration of exposure:
24 hours.
Doses:
2.0 g/kg bodyweight.
No. of animals per sex per dose:
A group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On
subsequent days the animals were observed once in the morning and again at the end of the experimental day. Clinical signs were recorded at each observation.

The treated areas of skin were examined daily for signs of dermal irritation and assessed according to the below scoring system (see Erythema and Eschar Formation).

A separate record was kept of dermal changes other than erythema and oedema.

The following were recorded on the study:
- The nature, severity approximate time of onset and duration of each toxic sign.
- Individual bodyweights of rats on Days 1 (day of dosing), 8 and 15



- Necropsy of survivors performed: All animals on the study were killed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs when present was recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths among ten rats subjected to a single occluded dermal application of D.I.X.T at 2.0 g/kg bodyweight.
Clinical signs:
There were no clinical signs of systemic reaction to treatment.
Body weight:
Low bodyweight gains were recorded on Day 8 for four female rats and on Day 15 for three of the same animals and one other female (see Table 2 - attached background material).
Gross pathology:
Terminal autopsy findings were normal.
Other findings:
Dermal Responses (see Table 1 - attached background material):
Slight or well-defined erythema was apparent on Days 2, 3 and 4 at the sites of application of the test substance. No other irritation reactions or dermal changes were observed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute lethal dermal dose to rats of D.I.X.T was found to be greater than 2.0 g/kg bodyweight.
Executive summary:

Introduction:

The experimental procedure was based on that recommended under Annex V of EEC directive 79/831/EEC, Part B Methods for determination of toxicity. Method B3, Acute Dermal Toxicity, and the OECD guideline for Testing of Chemicals No. 402 "Acute Dermal Toxicity".

Method:

A group of ten rats (five males and five females) were treated at 2.0 g/kg bodyweight for a 24 hour exposure period.

Clinical signs, dermal irritation, bodyweight development were monitered during the study. All animals were killed on Day 15 and subjected to a macroscopic post mortem examination.

Results:

Mortality:

There were no deaths among ten rats subjected to a single occluded dermal application of D.I.X.T at 2.0 g/kg bodyweight.

Clinical signs:

There were no clinical signs of systemic reaction to treatment.

Dermal responses:

Slight or well-defined erythema was apparent on Days 2, 3 and 4 at the sites of application of the test substance. No other irritation reactions or dermal changes were observed.

Bodyweight:

Low bodyweight gains were recorded on Day 8 for four female rats and on Day 15 for three of the same animals and one other female.

Terminal autopsy:

Terminal autopsy findings were normal.

Conclusion:

The acute lethal dermal dose to rats of D.I.X.T was found to be greater than 2.0 g/kg (>2000 mg/kg) bodyweight.