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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Study initiated 27 November 1984 (application of test material)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, equivalent to a valid guidelines and the study was conducted under GLP conditions. The study was performed with test material being used to support the substance on the basis of read-across.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): salicylic acid cyclohexyl ester (abbreviated as SCH)
- Molecular formula (if other than submission substance): C13H16O3
- Molecular weight (if other than submission substance): 220.27
- Smiles notation (if other than submission substance): C(=O)(c1c(O)cccc1)OC1CCCCC1
- Physical state: colourless liquid

Test animals

Species:
rabbit
Strain:
other: Small Russian Chbb: HM
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Karl Thomae GmbH Biberach
- Weight at study initiation: 2286 g (males); 2156 g (females)
- Diet: Altromin standard diet 2023 ad libitum
- Water: tap water ad libitum
- Acclimation period: 4 days for females, males had been held in the laboratory for two months prior to test initiation (20.09.1984).

ENVIRONMENTAL CONDITIONS
- Temperature: 20-21 °C:
- Humidity: 45-50 %:
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: aqueous suspension of 2 % carboxymethyl cellulose and 0.5 % cremophor
Details on dermal exposure:
TEST SITE
- Area of exposure: 150-170 cm²
- % coverage: approximately 10 %
- Type of wrap if used: double-layer gauze bandage covered with polyethylene film and then an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the bandages were removed and resides of the applied preparation washed off
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4g/kg

VEHICLE
- Concentration (if solution): The test material was prepared as a 50 % preparation.
- Justification for choice of vehicle: 50 % preparation of the test material was prepared with an aqueous suspension of 2 % carboxymethyl cellulose and 0.5 % cremophor with equal parts of the diluting agent and test material mixed together. The test material was dosed in a vehicle as neat applications of the test material demonstrated poor adherence to the skin and restlessness in the test animals in preliminary tests.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1, 2, 3, 4 and 6 hours after application and then twice daily (intoxicating effects); end of application and 2, 3, 6, 10 and 14 days after application (local reactions assessed according to the Draize scale); 1 hour before application and 24 hours, 7 and 14 days after application (body weights)
- Necropsy of survivors performed: yes and internal organs assessed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None.
Clinical signs:
In three females and one male, a slight reduction in body temperature was recorded during the initial six hours after application. Within the six hours after application, all animals exhibited slightly reduced activity. This was not observed after the removal of the bandage. Immediately after application, all animals exhibited slightly increased respiratory frequency. This was resolved by one hour after application. Twenty-four hours after the removal of the bandage, one male and four females, and after a further 24 hours, three males and all females, exhibited scratches and bite marks on the area of treated skin which they were considered to have inflicted on themselves. No general symptoms of intoxication were observed, 24, 48 and 72 hours, 6, 8, 9, 10, 13 and 14 days after application.
Body weight:
Slight weight loss occurred during application and no significant weight gain was considered to have occurred (see table 2). The weight loss was attributed to the limited mobility caused by the bandage.
Gross pathology:
The application area was variable in hairiness, but featured no special characteristics; this was likewise the case for the hypoderm and corresponding lymph nodes. The G.I. tract was on the whole well-filled, the respiratory tract and the parenchyma organs did not feature any special characteristics. The same was true for the reproductive organs. The pathological/anatomical findings for all test animals 14 days after treatment did not yield any peculiarities.
Other findings:
LOCAL REACTIONS
While the test material was being spread onto the skin, a slight erythema occurred across the entire area of treated skin, which could be assessed according to the Draize scale as being classification 1 for erythema. Oedema of the skin was not determined. Immediately after the bandage was removed and the residues of the applied preparation were washed off, a distinct erythema was determined for all animals, however no swellings of the skin were observed. Twenty-four hours after the bandage was removed, an intensification of the erythema was observed for one female. For one male, a reduction in the reactions was determined. However, for the remaining animals, the reactions remained constant in their intensity. Five days after application, the acute symptoms of inflammation had completed subsided for all of the animals, however severe desquamation of the treated skin was apparent, in particular in the back area. This desquamation only healed towards the end of testing (from the 12th test day).

Any other information on results incl. tables

Table 2: Bodyweights

     Body weight (g)   
 Animal no.  Sex  before application  24 h after application  7 d after application  14 d after application
 298  F  2200  2170  2240  2200
 300 F 2130   2080  2150  2100
 303  F  2100  2110  2150  2200
 305  F  2170  2160  2190  2120
 306  F  2180  2160  2200  2200
 197  M  2250  2180  2220  2160
 198  M  2380  2300  2300  2260
 199  M  2250  2230  2280  2160
 200  M  2250  2270  2260  2160
 202  M  2300  2330  2290  2190

Table 2: Skin reactions (assessed according to the Draize scale)

Animal no.

Sex

Immediately

Hours after application

Days after application

1

24

48

120

6 to 9

12

13

Reaction

E

O

E

O

E

O

E

O

E

O

E

O

E

O

E

O

298

F

2

0

2

0

2

0

2

0

0*

0

0*

0

0*

0

0*

0

300

F

2

0

2

0

2

0

2

0

0*

0

0*

0

0*

0

0*

0

303

F

2

0

2

0

3

0

2

0

0*

0

0*

0

0*

0

0*

0

305

F

2

0

2

0

2

0

1

0

0*

0

0*

0

0*

0

0*

0

306

F

2

0

2

0

2

0

2

0

0*

0

0*

0

0*

0

0*

0

197

M

2

0

1

0

1

0

1

0

0*

0

0*

0

0*

0

0*

0

198

M

2

0

2

0

2

0

1

0

0*

0

0*

0

0*

0

0*

0

199

M

2

0

2

0

2

0

1

0

0*

0

0*

0

0*

0

0*

0

200

M

2

0

2

0

2

0

1

0

0*

0

0*

0

0*

0

0*

0

202

M

2

0

2

1

2

0

2

0

0*

0

0*

0

0*

0

0*

0

* Distinct desquamation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test, the acute dermal LD50 of the test material was determined to be >2000 mg/kg bw in the rabbit.
Executive summary:

The acute dermal toxicity of the test material was determined under GLP conditions to the standardised guideline EU Method B3. During the study 5 male and 5 female rats were dosed dermally with a single administration of a 50% preparation of the test material. Animals were dosed at 2000 mg/kg and were observed for a period of 14 days post administration for mortality, body weights and clinical signs. Fourteen days following test material administration animals were sacrificed and an assessment of the internal organs was performed. Under the conditions of the study no mortality was observed. Limited clinical signs were seen and local reactions included erythema classified as 1 on the Draize scale up to five days after application however severe desquamation of the treated skin was apparent, in particular in the back area which only healed towards the end of testing. The LD50 of the test material was determined to be >2000 mg/kg bw.

The test material is considered sufficiently similar to (z)-3-hexenyl salicylate on the basis of read-across such that the results from this study can be used to address the acute dermal toxicity of (z)-3-hexenyl salicylate.