(Z)-3-hexenyl salicylate

Acute Toxicity: dermal

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

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

25485-88-5

Cas Number:

25485-88-5

IUPAC Name:

25485-88-5

Constituent 2

Reference substance name:

Benzoic acid, 2-hydroxy-, cyclohexyl ester

IUPAC Name:

Benzoic acid, 2-hydroxy-, cyclohexyl ester

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 or test system 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:

other: 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 rem

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.