(Z)-3-hexenyl salicylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 April 1984 to 27 August 1984

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:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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)
- Physical state: colourless liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, WIGA GmbH, Sulzfeld, Germany
- Fasting period before study: animals were fasted for 16 hours before dose administration and up to 3 hours following dose administration
- Housing: 5 animals per cage, by dose group
- Housing: Makrolon 3 cages
- Diet: Altromin standard diet 1324, Altromin GmbH, 4937 Lage, Germany ad libitum
- Water: tap water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: approximately 21 °C
- Humidity: approximately 51 %
- Photoperiod: 12 hours dark / 12 hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Arachidic oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 % (2000 mg/kg), 25.1 % (2510 mg/kg), 31.6 % (3160 mg/kg), 39.8 % (3980 mg/kg)
- Amount of vehicle (if gavage): 10 mL/kg

Doses:

2000, 2510, 3160 and 3980 mg/kg

No. of animals per sex per dose:

10 males and 10 females per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for symptoms and mortality were performed several times on the day of dose administration, then twice daily thereafter. Body weights were recorded on the day before dosing, on the day of dosing and then on days 2, 7 and 14
- Necropsy of survivors performed: yes; an assessment of the internal organs was performed.

Statistics:

According to the Behrens - Reed- Muench method, Drug and Chemical Toxicology (1981) 4: 297-305

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

3 339 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 912 - <= 3 829

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

3 031 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 499 - <= 3 677

Mortality:

Seven 3980 mg/kg males died on day 1, a further male died on day 2. Two days after dose administration four 3160 mg/kg males and one 2510 mg/kg male died. All of the male animals dosed at 2000 mg/kg survived until the end of the study. Two days following dose administration nine 3980 mg/kg females, five 3160 mg/kg females and two 2510 mg/kg females died. One 2000 mg/kg female died seven days following dose administration. All remaining animals survived until the end of the study (see table 1 for further information).

Clinical signs:

other: Clinical signs that were recorded during the study included unkempt coat, reduced activity, atony, emaciation, prone position and increased respiratory frequency (see Table 3 for further information).

Gross pathology:

Pathological findings included gastroesophageal erosions, pinky red spleen and hyperaemia at the knee joints in the 3980 mg/kg dose group; pinky red spleen, hyperemia at the knee joints in the 3160 mg/kg dose group and diarrhoea pulmonary oedema and hyperemia at the knee joints in the 2510 mg/kg dose group.

Any other information on results incl. tables

Table 1: Mortality

Dose group (mg/kg)	Males				Females
	3980	3160	2510	2000	3980	3160	2510	2000
Dead animals after                      1 h	0	0	0	0	0	0	0	0
1 d	7	0	0	0	0	0	0	0
2 d	8	4	1	0	9	5	2	0
7 d	8	4	1	0	9	5	2	1
14 d	8	4	1	0	9	5	2	1

Table 2: Body Weights

Dose group (mg/kg)	Males				Females
	3980	3160	2510	2000	3980	3160	2510	2000
1 d	212	212	217	209	177	186	181	180
start of testing	198	197	202	196	164	168	167	168
2 d	168	195	201	212	156	162	163	172
7 d	206	254	248	253	188	205	199	197
14 d	274	312	300	302	217	230	236	216

Table 3: Clinical Signs

Males
Dose group (mg/kg)	3980	3160	2510	2000
Unkempt coat	30 min - 3 h (10)		30 min - 3 h (10)	30 min (1)
Reduced activity			1 - 3 h (10)	1 d (1)
In prone position				1 d (1)
Increased respiratory frequency				1 d (1)
Found dead	1 d (7)	2 d (4)	2 d (1)
	2 d (1)
Females
Dose group (mg/kg)	3980	3160	2510	2000
Unkempt coat	30 min - 3 h (10)		30 min - 3 h (10)
Reduced activity	1-3 h (1)	3.5-6.5 h (1)	1-3 h (10)	1 d (2)
Atony, Emaciation	1 d (1)
In prone position	1 d (1)		1-3 h (1)	1 d (2)
Increased respiratory frequency	1 d (1)			1 d (1)
Found dead	1 d (1)	2 d (5)	2 d (2)	2 d (1)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the test, the acute oral LD50 was determined to be 3339 mg/kg in males rats and 3031 mg/kg in female rats.

Executive summary:

The acute oral toxicity of the test material was determined under GLP conditions to the standardised guideline OECD 401. During the study 10 male and 10 female rats were dosed orally, by gavage, with a single administration of test material in arachidic oil. Animals were dosed at 2000, 2510, 3160 and 3980 mg/kg and were observed for a period of 14 days post administration for mortality and clinical signs; body weights were also recorded. Fourteen days following test material administration animals were sacrificed and an assessment of the internal organs was performed. Under the conditions of the study seven 3980 mg/kg males died one day following dose administration, a further male died on day 2. Two days following dose administration four 3160 mg/kg males and one 2510 mg/kg male died. All of the male animals dosed at 2000 mg/kg survived until the end of the study. Two days following dose administration nine 3980 mg/kg females, five 3160 mg/kg females and two 2510 females mg/kg died. One 2000 mg/kg female died seven days after dose administration. All remaining animals survived until the end of the study. The LD50 of the test material was subsequently determined to be 3339 mg/kg in males and 3031 mg/kg in females.

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 oral toxicity of (z)-3-hexenyl salicylate.