Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 November 1992 to 19 November 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Appearance: Light yellow liquid, Clear Liquid
- Stability: There was no apparent change in the physical state of the test material during administration
- Storage conditions of test material: Room temperature, protected from exposure to light

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: pre-test weight range was 2.2 to 2.4 kg for males and 2.1 to 2.3 kg for females
- Housing: One per cage in suspended wire mesh cages. Bedding was placed beneath the housing and changed twice per week.
- Diet: Fresh diet was provided daily
- Water: ad libitum
- Acclimation period: At least one week in quarantine

ENVIRONMENTAL CONDITIONS
- Temperature: Temperature controlled; value not reported
- Photoperiod: 12 hour dark/light cycle

IN-LIFE DATES
From: 20 October 1992

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area of the trunk (intact skin)
- % coverage: Approximately 10 % of the body surface
- Type of wrap if used: The test site was covered with a gauze patch, secured with non-irritating tape and gentle pressure was applied to the gauze to aid the distribution of the test material over the area. The torso was wrapped with plastic which was secured with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test material was gently washed off with distilled water prior to dermal observations.
- Time after start of exposure: At 24 hours the patches were removed

TEST MATERIAL
- Amount(s) applied: The dose was based on the sample weight as calculated from the specific gravity
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 hours post dosing and once daily up to 14 days. Body weights were recorded pre-test, weekly and at death or termination. The animals were observed twice daily for mortality. The test sites were scored for dermal irritation at 24 hours post dose and on days 7 and 14 using the numerical Draize scale.
- Necropsy of survivors performed: Yes. All animals were examined for gross pathology. Abnormal tissues were preserved in 10 % buffered formalin for possible future examination.
Statistics:
The LD50, 95 % confidence limits, dose response curve and slope were calculated, if possible, by the method of Litchfield and Wilcoxon.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Nine out of ten animals survived the 2000 mg/kg dermal application. One male rabbit died on day 12.
Clinical signs:
The animal that died on day 12 exhibited pre-death physical signs of diarrhoea, lethargy and few faeces.
The nine out of ten animals that survived the 2000 mg/kg dermal application experienced instances of diarrhoea. Dermal reactions, absent to well defined on day 1 were absent on days 7 and 14.
Body weight:
Body weight changes were normal in all survivors.
Gross pathology:
Necropsy of the dead animal revealed abnormalities of the treated skin, lungs, pleural cavity and gastrointestinal tract. The death did not appear to be related to the treatment with the test material but to a pulmonary infection.
Necropsy results were normal in eight out of the nine surviving rabbits. One female exhibited liver abnormalities (nodules on liver).

Any other information on results incl. tables

Table 1: Body weight, dose volume and dermal reactions

Ear tag # & Sex

Dose volume (cc)

Body Weight (kg) on Day

Skin Reactions on Day

% Rem.

1

7

14

1

7

14

E

O

E

O

E

O

D4973-M

3.9

2.3

2.4

2.6

1a

2

0*

0

0*

0

70

D4969-M

4.1

2.4

2.1†

-

2a

2

0*

0

-

-

60

D4967-M

4.1

2.4

2.5

2.7

1a

1

0

0

0

0

40

D4971-M

3.9

2.3

2.3

2.4-

1a

1

0*

0

0*

0

50

D4963-M

3.7

2.2

2.3

2.3

1a

1

0

0

0

0

50

Mean

2.3

2.3

2.5

 

SD

0.08

0.15

0.18

Number

5

5

4

D5020-F

3.5

2.1

2.3

2.4

0a

0

0

0

0

0

40

D5011-F

3.5

2.1

2.3

2.4

1a

0

0f*

0

0

0

35

D5013-F

3.9

2.3

2.4

2.5

0a

0

0

0

0

0

40

D5017-F

3.9

2.3

2.4

2.6

0a

0

0*

0

0*

0

40

D5014-F

3.5

2.1

2.2

2.3

0a

0

0

0

0

0

35

Mean

2.2

2.3

2.4

 

SD

0.11

0.08

0.11

Number

5

5

5

†Body weight verified. This animal died on day 12 with a terminal body weight of 1.9 kg

E = erythema (redness)

O= oedema

a = dose site stained yellow

f = flaking skin

* = animal re-clipped

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

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of this study, the LD50 value was found to be greater than 2000 mg/kg of body weight.
Executive summary:

The potential of the test material to cause acute dermal toxicity in the rabbit was investigated in accordance with the standardised guideline OECD 402 under GLP conditions.

Five healthy male and five healthy female New Zealand Albino rabbits were dosed dermally with the test material at 2000 mg/kg of body weight. The test material was applied to intact skin and covered in an occlusive fashion for 24 hours. at the end of the exposure period, the test material was gently washed off with distilled water.

Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 hours post dosing and once daily up to 14 days. Body weights were recorded pre-test, weekly and at death or termination. The animals were observed twice daily for mortality. The test sites were scored for dermal irritation at 24 hours post dose and on days 7 and 14 using the numerical Draize scale. All animals were examined for gross pathology.

Nine out of ten animals survived the 2000 mg/kg dermal application. One male rabbit died on day 12 and exhibited pre-death physical signs of diarrhoea, lethargy and few faeces.

The nine out of ten animals that survived the 2000 mg/kg dermal application experienced instances of diarrhoea. Dermal reactions, absent to well defined on day 1 were absent on days 7 and 14. Body weight changes were normal in all survivors.

Necropsy of the dead animal revealed abnormalities of the treated skin, lungs, pleural cavity and gastrointestinal tract. The death did not appear to be related to the treatment with the test material but to a pulmonary infection. Necropsy results were normal in eight out of the nine surviving rabbits. One female exhibited liver abnormalities (nodules on liver).

Under the conditions of this study, the LD50 value was found to be greater than 2000 mg/kg of body weight.