Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 10 Jan 1985 to 24 Jan 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to OECD Guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
6 rabbits (4 males, 2 females) were used for this study. Skin application site was abraded on 50% of the animals to enhance dermal penetration
GLP compliance:
no
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): MT-178
- Substance type: pure active substance
- Lot/batch No.:
- Expiration date of the lot/batch:
- Storage condition of test material: The test article was stored at ambient room temperature

Test animals

Species:
rabbit
Strain:
other: albino rabbits
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals USA
- Age at study initiation: no data
- Weight at study initiation: 2.2 - 2.5 kg
- Fasting period before study:
- Housing: animals were housed 2/cage in suspended wire mesh cages. Bedding was placed beneath the cages.
- Diet (e.g. ad libitum): ad libitum, Fresh Purina Rabbit Chow (Diet #53-21)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: 10 Jan 1985 To: 24 Jan 1985

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: abdomen
- % coverage: ca. 10 % of body surface
- Type of wrap if used: The test article was covered with a gauze patch and gentle pressure was applied to the gauze to aid the distribution of the test article over the prepared site. The torso was wrapped with plastic which was secured with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): application site was wipped
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/kg bw
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg (male and female)
No. of animals per sex per dose:
4 males + 2 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animal were observed daily. Bodyweights were recorded pretest and at termination of the test.
- Necropsy of survivors performed: yes
- Other examinations performed: toxicity and pharmacological effects, body weight, gross pathology
Statistics:
The LD 50 and 95% Confidence were calculated, if possible, by the method of Litchfield, J.T. Jr., & F. Wilcoxon JPET 96:99, 1949 or Horn, H.J. Biometric.s 12:311, 1956.

Results and discussion

Preliminary study:
Not Applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no death
Clinical signs:
There were no signs of toxicity.
Physical signs: Three animals were normal during the 14 day observation period. Instances of few feces and yelllow nasal discharge were noted in the remaining three animals.
Body weight:
All animals showed expected gains in bodyweight over the study period
Gross pathology:
All animals were normal

Any other information on results incl. tables

Table 1: bodyweight, dose volume and dermal reactions

Rabbit # & sex

Dose volume cc

Weight (kg) day 0

Weight (kg) day 14

Day 1

Day 7

Day 14

% remaining

R

E

R

E

R

E

1-M ab

5.3

2.5

2.9

2

2

0 f

0

0

0

20

2-M

4.7

2.2

2.6

2

2

4

0

0

0

20

3-M ab

4.9

2.3

2.5

2 gb

2

4

2

0

0

20

4-M

4.9

2.3

2.7

2

0

0 f

0

0

0

20

5-F ab

4.9

2.3

2.7

3

2

4

1

0 f

0

20

6-F

4.7

2.2

2.8

2

2

0

0

0

0

20

 

Codes used:

R =erythema(redness)

E. =edema

ab=abraded

b = brown areas

f =flaking skin

g =green areas

% remaining = the amount of material remaining on the skin, gauze and occlusive binding at 24 hours, after the occlusive binding was removed.

 

DERMAL SCORING CODE for EVALUATION OF SKIN REACTIONS

 

ERYTHEMA & ESCHAR FORMATION:

0             NO ERYTHEMA

1             VERY SLIGHT ERYTHEMA (BARELY PERCEPTIBLE)

2             WELL DEFINED ERYTHEMA

3             MODERATE TO SEVERE ERYTHEMA 3

4             SEVERE ERYTHEMA (BEET REDNESS) TO SLIGHT ESCHAR FORMATION (INJURIES IN DEPTH)

EDEMAFORMATION:

0             NO EDEMA

1             VERY SLIGHT EDEMA (BARELY PERCEPTIBLE)

2             SLIGHT EDEMA (EDGES OF AREA WELL DEFINED BY DEFINITERAISING)

3             HODERATE EDEMA (RAISED APPROXIMATELY 1 MILLIMETER)

4             SEVERE EDEMA (RAI SED MORE THAN 1 MI LLIMETER AND EXTENDING BEYOND THE AREA OF EXPOSURE)

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD 50 is greater than 2.0 g/kg of body weight.
Executive summary:

Purpose of the study. The purpose of this study was to investigate the toxicity of the test article in the albino rabbit. The procedures used were equivalent to the OECD Guideline 402 on Acute Dermal Toxicity with two deviations (see below under Methods).

Method. Six healthy albino rabbits were dosed dermally in a limit test with a unique concentration of test material at a dose level of 2000 mg/kg of body weight.

Two deviations were made from the OECD Guideline: 1.) 6 animals (4 males, 2 females) were used for the study instead of 10; 2.) skin application site was abraded on 50% of the animals to enhance dermal penetration.

The test article was kept in contact with the skin for 24 hours. The animals were observed daily for signs of mortality, toxicity and pharmacological effects. Skin reactions were scored on Days 1, 7 and 14. Body weights were recorded pretest and at termination. All animals were examined for gross pathology.

Results. All animals survived the 2000 mg/kg dermal application. Physical signs of few feces and yellow nasal discharge were noted during the study. Body weight changes were normal. Dermal reactions, slight to moderate on Day 1, were absent to severe on Day 7 and absent on Day 14. Necropsy results were normal.

Discussion. Study was performed using occlusive patch and skin abrasion was used in that study to increase dermal penetration and exposure. As exposure to test substance was not lethal both on more severe conditions (abreded skin, occlusive patch) and as dermal reactions were completely reversible effect after 14 days, it can be concluded that the test substance has no toxic effect on test animals despite a lower number of animals used in the study.

Conclusion. The LD50 is greater than 2000 mg/kg of body weight.