Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5th March 1993 to 16th June 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline studies with restrictions. Information relating to the test animals, exposure and test system were not described in the main body of the report but were given in the protocol only.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

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
Qualifier:
according to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 97.3%
Batch No.: 9236-23

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS (information given in the study protocol)
- Source: Iffa-Credo BP 0109 (69592 L'Arbresle Cedex - France)
- Age at study initiation: adult 5 to 7 weeks old
- Weight at study initiation: Males: 252-278 g; Females: 226-244 g
- Fasting period before study: Not specified
- Housing: Animals housed individually in polycarbonate cages type Fl (305 x 180 x 184 mm). Bedding was dust-tree sawdust made from spruce tree wood, analysed twice a year for chemical and bacterial contaminants.
- Diet (e.g. ad libitum): Pelleted complete diet available ad libitum (rat-mouse Diet reference AO4 C10, Usine d'Alimentation Rationnelle, Villemoisson s/Orge, France)
- Water (e.g. ad libitum): Filtered (0.2 µm) mains drinking water available ad libitum.
- Acclimation period: Minimum of 5 days

ENVIRONMENTAL CONDITIONS (information given in the study protocol)
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30-70%
- Air changes (per hr): Minimum 8 air changes per hour
- Photoperiod: 12 hours light (artificial)/12 hours dark

IN-LIFE DATES: Not specified

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: Sterile Codex liquid paraffin
Details on dermal exposure:
TEST SITE (information given in the study protocol)
- Area of exposure: The day before the application of the test article, the back and the flanks of each animal were carefully clipped, to expose an area of skin which should not be less than 10 % of the total body surface area.
- % coverage: The test article was applied so that it formed a film as thin and as uniform as possible (% coverage not specified).
- Type of wrap if used: The semi-occlusive bandage covered fully the treated area, in order to prevent ingestion of the test article.

REMOVAL OF TEST SUBSTANCE (information given in the study protocol)
- Washing (if done): At the end of the 24 hour period, the binders were removed and the skin wiped clean of residual test article using water or other convenient means.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): See below
- Concentration (if solution): Not applicable
- Constant volume or concentration used: Not specified
- For solids, paste formed: Yes (pH = 5.7)

VEHICLE
- Amount(s) applied: 4.199 mL/kg bw of test material in the vehicle
- Concentration: 47% test article in the vehicle
- Batch no.: T8810B
- Purity: Not specified
Duration of exposure:
24 h
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: 14 days
- Frequency of observations and weighing: Examinations for mortality and abnormal clinical signs were performed 15 minutes after application, then at 1, 2 and 4 hours, and then daily for the 14 day study period. Cutaneous examinations were performed from day 2 to 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: All the animals were weighed, immediately before application of the test article (Day 1), on Days 8 and 15.
Statistics:
No data available

Results and discussion

Preliminary study:
Not performed
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
There were no changes in behaviour or clinical signs in any of the treated animals during the observation period.
The local tolerance of the test article was good; no cutaneous lesion (erythema or oedema) was noted to the application site of the test article during the observation period. Desquamation was noted in one male from Day 5 to Day 7.
Body weight:
Body weight changes in the treated animals were not influenced by treatment.
Gross pathology:
There were no macroscopic findings that could be associated with treatment.
Other findings:
None reported

Applicant's summary and conclusion

Interpretation of results:
other: EU-GHS criteria not met
Conclusions:
From the results obtained under the experimental conditions employed, the LD 50 by the cutaneous route in the rat (male + female) is >2000 mg/kg.
Executive summary:

The test material, Millad®3988, was evaluated for its acute dermal toxicity potential in male and female rats following a single cutaneous application at a dose level of 2000 mg/kg bw. The estimated dermal LD50 values for male and female rats were determined to be greater than 2000 mg/kg bw. All animals appeared normal and exhibited body weight gain throughout the study. The gross necropsy examinations at termination revealed no macroscopic findings that could be associated with treatment.