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Toxicological information

Repeated dose toxicity: inhalation

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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:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Methyl salicylate manufactured by ICI, UK. No other details available

Test animals

Species:
rat
Strain:
other: Alderley Park
Sex:
female
Details on test animals 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

open allclose all
Dose descriptor:
NOAEC
Effect level:
700 mg/m³ air (nominal)
Basis for effect level:
other: overall effects, no adverse effects. Values for methyl salicylate.
Dose descriptor:
NOAEC
Effect level:
1 207 mg/L air (nominal)
Basis for effect level:
other: read-across value for homosalate

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 1207 mg/m³ of homosalate.
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).