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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP study in accordance with EU Method B.1. To address toxicological endpoints as part of the REACH registration of Benzyl Salicylate (Target Substance) it is proposed to read-across to Cyclohexyl Salicylate (Source Substance). The use of read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible. The Target Substance and Source Substance have been characterised using the categories and databases present in the OECD [Q]SAR Toolbox. From the profiling, it can be seen that the two substances share structural similarities and also ‘mechanistic action’ similarities which are both general and endpoint specific. Therefore read across is justified.

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
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Salicylsäurecyclohexylester
- Physical state: colourless liquid
- Analytical purity: 98.5%
- Impurities (identity and concentrations): not reported
- Purity test date: not reported
- Lot/batch No.: S 010
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not reported
- Storage condition of test material: not reported

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
- Age at study initiation: not reported
- Weight at study initiation: average body weight of males was 209 to 217 g, average body weight of females was 164 to 168 g
- Fasting period before study: yes, 16 hours prior to and 3 hours after exposure
- Housing: 5 animals per Makrolon 3 cage, softwood bedding
- Diet (e.g. ad libitum): Altromin rodent diet 1324 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 51
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Remarks:
DAB 8
Details on oral exposure:
VEHICLE
- Concentration in vehicle: depending on dose level 20 to 39.8% (g/v)
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: not reported
- Lot/batch no. (if required): 30809, Caesar and Loretz, Hilden

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000, 2510, 3160 and 3980 mg/kg
No. of animals per sex per dose:
10 males/10 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for clinical signs and mortality several times on day of application, then 2 times per day for observation period; body weight was recorded one day before application, on day of application, and 2, 7 and 14 days after application
- Necropsy of survivors performed: yes
Statistics:
According to Behrens and Reed-Muench (1981), Drug and Chemical Toxicology 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:
see attached table on mortality
Clinical signs:
Scrubby posture, lowered activity, increased breathing frequency, face-down position, atony
Body weight:
No significant findings reported
Gross pathology:
2510 mg/kg dose group: diarrhoe, lung oedema, hyperemia in the area of the knee joints
3160 mg/kg dose group: reddish spleen, hyperemia in the area of the knee joints
3980 mg/kg dose group: suspected erosion of the forestomach, reddish spleen, hyperemia in the area of the knee joints (pineal gland of the tibiae, femora and patella)

Any other information on results incl. tables

Table: Mortality of animals

Cumulative number of dead male animals (n= 10 per dose group)

Time point of observation

3980 mg/kg

3160 mg/kg

2510 mg/kg

2000 mg/kg

1 hour

0

0

0

0

1 day

7

0

0

0

2 days

8

4

1

0

7 days

8

4

1

0

14 days

8

4

1

0

Cumulative number of dead female animals (n= 10 per dose group)

Time point of observation

3980 mg/kg

3160 mg/kg

2510 mg/kg

2000 mg/kg

1 hour

0

0

0

0

1 day

0

0

0

0

2 days

9

5

2

0

7 days

9

5

2

1

14 days

9

5

2

1

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 value of cyclohexyl salicylate was greater than 2000 mg/kg in an acute oral toxicity study with male and female Sprague-Dawley rats.
Executive summary:

The oral acute toxicity of the substance cyclohexyl salicylate to young adult male and female Sprague-Dawley rats was studied under GLP in accordance with EU Method B.1. The substance was dissolved in peanut oil DAB 8 and administered to rats after a fasting period of 16 hours at a volume of 10 mL/kg once by oral gavage at doses of 2000, 2510, 3160 and 3980 mg/kg. Ten male and ten female animals per dose group were then observed for a period of 14 days. The mortality rate was found to be dose-dependent: 8 males and 9 females in the group receiving 3980 mg/kg were found dead on day 2 after dosing, whereas 4 males and 5 females in the group receiving 3160 mg/kg were found dead on day 2 after dosing. One male and two females receiving 2510 mg/kg and no male and one female receiving 2000 mg/kg were found dead during the observation period. Clinical and pathological findings in animals found dead included scrubby posture, lowered activity, increased breathing frequency, face-down position, atony, diarrhoe, lung oedema, hyperemia in the area of the knee joints (pineal gland of the tibiae, femora and patella), suspected erosion of the forestomach, reddish spleen. The calculated LD50 value was 3339 mg/kg in males and 3031 mg/kg in females.