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Toxicological information

Acute Toxicity: oral

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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:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

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)
- Physical state: colourless liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
3 339 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 912 - <= 3 829
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:
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).
Body weight:
All animals gained weight during the study. There was a slight depression of body weight following dose administration (see table 2 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.