Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8 to 22 May 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to OECD guidelines (with certain deviations)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
groups of two animals per sex tested, instead of the indicated five of a single sex. Patch was occluded, rather than semi-occluded
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MRD-80-22
- Substance type: technical product
- Physical state: dark amber liquid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Dutchland Laboratory Animals Inc., Denver, Pennsylvania
- Age at study initiation: "young adults"
- Weight at study initiation: 2.2-2.6 kg
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 17 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-20
- Humidity (%): no data ("monitored daily")
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 8 May 1980 To: 22 May 1980

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and ventral surface from scapular to pelvic area
- % coverage: 20% of body surface
- Type of wrap if used: gauze covered with an impervious plastic sleeve secured with masking tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped free of excess test substance; no washing
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.044, 0.175, 0.696 or 2.772 ml/kg bw
- Constant concentration used: yes, neat


Duration of exposure:
24 hr
Doses:
50, 200, 794 or 3160 mg/kg bw
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
observations for mortalities - twice daily;
clinical observations - 1, 2 and 4 h post-dosing, then daily;
body weights - day -1 (time of clipping), days 0, 7 and 14;
irritation - 30 min after removal of the patch
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and skin irritation (erythema and edema)
Statistics:
no data

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 160 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no CL given in the report
Mortality:
All animals survived
Clinical signs:
At 200, 794 and 3160 mg/kg bw, several animals had soft faeces and faecal staining on some days throughout the study; however the number of animals involved and frequency of occurrence were not dose-related.
Body weight:
One female each at 794 and 3160 mg/kg bw had lost 0.1 kg when weighed on day 7 compared to body weights on day 0. All animals had body weight gains at study termination compared to weights on day 0, except two females in the 794 mg/kg bw group who had no body weight change over the 14 days.
Gross pathology:
Changes observed occurred in the majority of animals at all dose levels, but their severity did not appear to be dose-related. These changes included diminished and roughened spleens, red or tan coloured lungs, vascularized stomach and/or intestines and red foci in the adrenals.
Other findings:
At the application site (30 minutes after patch removal), very slight to severe erythema (grade 1-3) was evident at 50 and 200 mg/kg bw, and moderate to severe erythema (grade 3) at 794 and 3160 mg/kg bw. Edema ranged from absent to very slight (grade 0-1) at the lowest dose, absent to well-defined (grade 0-2) at 200 mg/kg bw, very slight to well-defined (grade 1-2) at 794 mg/kg bw and well-defined (grade 2) at the highest dose.

Exfoliation of the skin was evident during the second week at the application site at the highest dose and skin necrosis was present in two of these animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No mortalities occurred up to 14 days after application of undiluted MRD-80-22 to the shaved skin of rabbits (2/sex/dose) at up to 3160 mg/kg bw under an occluded patch for 24 h.
Executive summary:

Test material MRD-80-22 was assessed for acute dermal toxicity in New Zealand White rabbits in a protocol similar to OECD guideline 402. Doses of the undiluted liquid were applied to the shaved skin of groups of two animals/sex at 50, 200, 794 or 3160 mg/kg bw under an occluded patch. After 24 hours, the patch was removed and the test site wiped free of excess test material. Observations were carried out during a 14-day period, after which the animals were subject to necropsy.

No deaths occurred during the study. At 200, 794 and 3160 mg/kg bw, several animals had soft faeces and faecal staining on some days throughout the study; however the number of animals involved and frequency of occurrence were not dose-related. All animals had gained in body weight at study termination, except two females at 794 mg/kg bw which showed no weight change. Changes observed at necropsy occurred in the majority of animals at all dose levels, but their severity did not appear to be dose-related. These changes included diminished and roughened spleens, red or tan coloured lungs, vascularized stomach and/or intestines and red foci in the adrenals. Erythema and edema was observed at all dose levels and tended to be dose-related in severity. Exfoliation of the skin was evident during the second week at the application site at the highest dose and skin necrosis was present in two of these animals.

In conclusion, under the test conditions, since the LD50 was considered >3160 mg/kg bw, MRD-80-22 would not be classified for acute dermal toxicity according to the EU CLP Regulations or the Dangerous Substances Directive.