Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Non-GLP study; however, GLP was not compulsory at the time the study was conduced, and the report contains signed QAU statement. The test conduct was in principle quite similar to the OECD TG 402, however with some deviations: - The number of animals used is lower than prescribed by the guideline, however, newer guidelines for acute toxicity studies use only 3 animals per sex and dose and therefore this reduced number should also be sufficient. - Only two dose levels were employed. Moreover, the test material is insufficiently characterized in the report, and no analytical purity was given. However, according to " Triclosan supplement I to EU dossier submitted 18 August 2009", the purity of CIBA-produced Triclosan exceeded 99%, and for FAT 80023/A, a degree of purity of 99.3% was reported. Despite of some deviations and deficiencies the study is scientifically acceptable and suitable for assessment.

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test was conducted according to the method of Noakes and Anderson (A method for determining the dermal toxicity of pesticides. Brit. J. Industr. Med. 26: 59-64, 1969), which was in general compliance with the OECD TG 402.
GLP compliance:
no
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): FAT 80023/A
- Physical state: powder
- Analytical purity: not specified; however, according to " Triclosan supplement I to EU dossier submitted 18 August 2009", the purity of CIBA-produced Triclosan exceeded 99%, and for FAT 80023/A, a degree of purity of 99.3% was reported.
- No further data provided

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: animals bred and raised on the premises
- Age at study initiation: young adult animals were used
- Weight at study initiation: 2 to 3 kg
- Housing: individually, in wire cages
- Diet (e.g. ad libitum): rabbit food - NAFAG, No. 814, Gossau SG, ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 14 hrs/10 hrs

Administration / exposure

Type of coverage:
occlusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
FAT 80023/A was suspended to achived the corresponding dosage level, using polyethylene glycol (PAG 400; Fluka AG) as vehicle.
Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
The application volume was 5 and 12 mL/kg bw
Duration of exposure:
24 hours
Doses:
0, 1000, 6000 mg/kg bw
No. of animals per sex per dose:
Three animals/sex/group were used
Control animals:
yes
Details on study design:
Approximatively 24 hours prior application, an area of the back of each test animal was shaved.
The test compound was applied onto the skin and the application site was covered with an occlusive dressing which was fastened around the trunk with an adhesive elastic bandage.
After 24 hours, the dressing was removed and the application site of each animal was cleaned with lukewarm water.
The skin reaction was assessed by means of the Draize scoring system.
Depending on the dose level, the animals were observed for up to14 or 21 days for mortality and clinical signs of toxicity.
The body weights were recorded immediately prior to dosing and after 7, 14 and 21 days.
At the end of the observation period, the animals were sacrificed for the purpose of necropsy.
Statistics:
The LD50 including 95% confidence limits was calculated by the Logit model

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 000 mg/kg bw
Mortality:
One male rabbit of the 6000 mg/kg bw group died on day 8 post exposure.
Clinical signs:
Compound-related clinical signs in the 1000 and 6000 mg/kg bw groups included sedation, dyspnoea, exophthalmos, ruffled fur, and curved body position. In addition, ataxia was noted in the 6000 mg/kg bw group only.
The animals of the control group showed no toxic symptoms.
In the 1000 mg/kg bw group, the animals recovered within 13 days; therefore, they were sacrificed on day 14 of observation.
In the 6000 mg/kg bw group, the animals recovered within 20 days; therefore, they were sacrificed on day 21 of observation.
Body weight:
For details, see table below.
Gross pathology:
Necropsy of the animals sacrificed at the end of the observation period revealed partially congested organs.
Other findings:
Skin irritation findings:
In the 1000 mg/kg bw group, skin examination revealed minimal to slight signs of irritation from day 1 to 13 post exposure (erythema with maximal mean score value of 1.3, and edema with maximal mean score value of 0.5)
In the 6000 mg/kg bw group, skin examination revealed minimal to moderate signs of irritation from day 1 to day 21 (erythema with maximal mean score value of 2.8 and edema with maximal mean score value of 2), and moderate necrosis formation was observed at the application site from day 6 to 19.

Any other information on results incl. tables

Mortality data:

 

Dose [mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

0

0/0/3

0

1000

0/3/3

day 1 - day 19

0

6000

1/3/3

day 1 - day 19

day 8

33.3

LD50 > 2000 mg/kg bw

 

Females

0

0/0/3

0

1000

0/3/3

day 1 - day 19

0

6000

0/3/3

day 1 - day 19

0

LD50 > 5000 mg/kg bw

* first number = number of dead animals

  second number = number of animals with signs of toxicity

  third number = number of animals used

Body weight changes:

FAT 80023/A, acute dermal toxicity in rabbits, body weight findings

Test dose

0

1000 mg/kg bw

6000 mg/kg bw

Mean body weight (kg), males (N=3)

Day 1

2.65 ± 0.15

2.53 ± 0.14

2.77 ± 0.15

Day 7

2.81 ± 0.02

2.53 ± 0.22

2.51 ± 0.01

Day 14

2.59 ± 0.01

2.56 ± 0.44

2.81 ± 0.06

Day 21

n.a.

n.a.

2.98 ± 0.03

Mean body weight (kg), females (N=3)

Day 1

3.16 ± 0.13

2.97 ± 0.26

2.91 ± 0.12

Day 7

3.21 ± 0.27

3.01 ± 0.31

2.87 ± 0.08

Day 14

3.20 ± 0.31

3.08 ± 0.31

3.05 ± 0.18

Day 21

n.a.

n.a.

3.22 ± 0.27

n.a., not applicable as sacrifice at day 14

Applicant's summary and conclusion