2-ethylhexyl salicylate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Single concentration tested. No data on substance purity.

Data source

Reference

Reference Type:

publication

Title:

Subacute inhalation toxicity of 109 industrial chemicals

Author:

Gage JC

Year:

1970

Bibliographic source:

Br J Ind Med 27:1-18

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl salicylate

EC Number:

204-317-7

EC Name:

Methyl salicylate

Cas Number:

119-36-8

Molecular formula:

C8H8O3

IUPAC Name:

Methyl 2-hydroxybenzoate

Test animals

Species:

rat

Strain:

other: Alderley Park

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Alderley Park
- Age at study initiation: no data
- Weight at study initiation: mean 200g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: Not applicable, vapour

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

7 hours per day, 5 days per week

Doses / concentrations

Remarks:

Doses / Concentrations:
700 mg/m3
Basis:
nominal conc.

No. of animals per sex per dose:

4

Details on study design:

not given

Positive control:

no data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Daily

FOOD CONSUMPTION: - No data

FOOD EFFICIENCY:- No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: Yes
- Time schedule for collection of urine: Overnight after last exposure
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

none

Statistics:

no data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

700 mg/m³ air (nominal)

Basis for effect level:

other: overall effects, no adverse effects. Values for methyl salicylate.

2

Dose descriptor:

NOAEC

Effect level:

1 155 mg/L air (nominal)

Basis for effect level:

other: read-across value for 2-ethylhexyl salicylate

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No toxic signs and no macroscopic or microscopic effects were seen at necropsy following exposure to a saturated atmosphere for 7 hours per day, 5 days per week for 4 weeks.

Applicant's summary and conclusion

Conclusions:

Methyl salicylate showed no evidence of toxicity by inhalation when tested at an effectively saturated concentration for 7 hours per day for four weeks. The highest tested concentration of methyl salicylate of 700 mg/m³ corresponds to 1155 mg/m³ of 2-ethylhexyl salicylate.

Executive summary:

4 female Alderley Park rats weighing an average of 200 g were exposed to a dynamic atmosphere (atmosphere continuously generated and passed through the exposure chamber) containing a saturated atmosphere (700 mg/m3) of methyl salicylate for 7 hours per day, 5 days per week for 4 weeks. Food and water were available ad libitum. Animals were weighed each day, and their condition and behaviour were recorded throughout the exposure period. Urine was collected overnight after the last exposure day for biochemical testing. Gross necropsy was conducted as well as microscopic examination of organs. Methyl salicylate at 700 mg/m3 (120 ppm), the maximum achievable atmosphere, did not cause any adverse effects (Gage, 1970).