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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Not documented
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Secondary source from public literature
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
The subacute inhalation toxicity of 109 industrial chemicals
Author:
Gage J C
Year:
1970
Bibliographic source:
Brit J Industr. Med, 1970, 27, 1-18
Report date:
1969

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Female rats were exposed for 7 hours daily via whole body inhalation chamber to 700mg/m3. 120ppm for a period of 20 days
GLP compliance:
not specified
Limit test:
yes

Test material

Constituent 1
Chemical structure
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 salicylate
Test material form:
other: liquid
Details on test material:
Name of test material (as cited in study report): Methyl Salicylate
Molecular formula: C6H4(OH)-2-COOMe
Physical state: liquid bp 223C

Test animals

Species:
rat
Strain:
other: Alderley Park
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Source: Specified pathogen free colony
Age at study initiation: Not documented
Weight at study initiation: Average 200g
Fasting period before study: Not documented
Housing: cages
DIET: ad libitum in housing cages
Water: ad libitum in housing cages
Acclimation period: Not documented

ENVIRONMENTAL CONDITIONS
Temperature: Not documented
Humidity: Not documented
Air changes: Not documented
Photoperiod (hrs dark/hrs light): Not documented

IN-LIFE DATES: Not documented

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Remarks on MMAD:
MMAD / GSD: Not determined
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
A nearly saturated vapour obtained by passing air through a liquid contained in a bubbler with a scintered glass air distributor disc. The volume of the liquid was usually 10-20ml and . if the size of the sample available permitted, it was replaced daily. The bubbler was maintained in a water bath at room temperature, about 20C

TEST ATMOSPHERE
- Brief description of analytical method used: The nearly saturated concentration prepared by method was estimated by weighing the sample before and after the day's run and relating the weight loss to the volume of air passing. This concentration expressed in milligrammes per litre was converted to parts per million on theassumption that the sample was pure.
- Samples taken from breathing zone: no

Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Not documented
Duration of treatment / exposure:
7 hour exposure, once daily for 20 days
Frequency of treatment:
7 hour exposure, once daily for 20 days
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
700mg/m3
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
120ppm
Basis:
nominal conc.
No. of animals per sex per dose:
4 females
Control animals:
not specified
Details on study design:
4 female rats were exposed for 7 hours daily via whole body inhalation chamber to 700mg/m3, 120ppm methyl salicylate, for a period of 20 days
- Dose selection rationale:
-The concentration was selected to produce, if possible, acute effects after short exposure and the exposure period was extended until the animals could survive 6-hour exposure, for up to 4 weeks
Positive control:
No information provided

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:throughout the exposure period
- Cage side observations checked conditions and behaviour

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations:each morning

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at sacrifice
- Anaesthetic used for blood collection: Yes (halothane)
- Animals fasted: No
- How many animals:All
- Parameters checked No data

CLINICAL CHEMISTRY: No data

URINALYSIS: Yes
- Time schedule for collection of urine: overnight
- Metabolism cages used for collection of urine: No data
- Animals fasted: No
- Parameters checked No data

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: No additional information
Sacrifice and pathology:
GROSS PATHOLOGY: Yes

The rats were anaesthetised with halothane and partially exsanguinated by heart puncture for haematological tests. After a gross examination of the organs, the lungs were inflated with formol-saline and immersed in the same fixative

HISTOPATHOLOGY: Yes



The following organs were also taken for microscopical examination after fixation in formol-corrosive: lungs, liver, kidneys, spleen and adrenals and occasionally heart, jejunum, ileum and thymus
Other examinations:
No additional information
Statistics:
No information provided

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 specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
not specified
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
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 specified
Details on results:
CLINICAL SIGNS AND MORTALITY: No effects, no further details given

BODY WEIGHT AND WEIGHT GAIN: No effects, no further details given

FOOD CONSUMPTION: No data

FOOD EFFICIENCY: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No effects, no further details given

CLINICAL CHEMISTRY: No data

URINALYSIS: No effects, no details given

NEUROBEHAVIOUR: No data

ORGAN WEIGHTS

GROSS PATHOLOGY

HISTOPATHOLOGY: NON-NEOPLASTIC

HISTOPATHOLOGY: NEOPLASTIC (if applicable)

HISTORICAL CONTROL DATA (if applicable)

OTHER FINDINGS
CLINICAL SIGNS AND MORTALITY: No effects, no further details given

BODY WEIGHT AND WEIGHT GAIN: No effects, no further details given

FOOD CONSUMPTION: No data

FOOD EFFICIENCY: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No effects, no further details given

CLINICAL CHEMISTRY: No data

URINALYSIS: No effects, no further details given

NEUROBEHAVIOUR: No data

ORGAN WEIGHTS: No effects, no further details given

GROSS PATHOLOGY: No effects, no further details given

HISTOPATHOLOGY: NON-NEOPLASTIC: No effects, no further details given

HISTOPATHOLOGY: NEOPLASTIC (if applicable): No data

HISTORICAL CONTROL DATA (if applicable): No information provided

OTHER FINDINGS: No further data

Effect levels

Dose descriptor:
NOAEL
Remarks:
>120ppm
Effect level:
> 700 mg/m³ air (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: no toxic signs: autopsy, organs normal

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No additional information

Applicant's summary and conclusion

Conclusions:
The results of this study with meythyl salicylate indicate that the no adverse effect level (NOAEL) is 120ppm via inhalation exposure for 7 hours daily for 20 days (equivalent to 700mg/m3). Due to the structural and functional similarities of hexyl and methyl salicylate, it is considered appropriate for the purposes of read-across
Executive summary:

In the study conducted by Gage (1974), the test substance, methyl salicylate, was examined for its ability to induce toxicity following repeated exposure for a period of 20 days. Female rats were exposed for 7 hours daily via whole body inhalation chamber to 700mg/m3 (120ppm), for a period of 20 days. Observations included conditions and behaviour, body weight, haematology, urinalysis, gross pathology and histopathological examinations.

No toxic signs were observed throughout the duration of the study and at autopsy, organs appeared normal. Under the conditions of this study, the no observed adverse effect level (NOAEL) was 120ppm via inhalation or circa 700mg/m3.

Due to the similar structural, physical and chemical properties of methyl salicylate, it was considered appropriate for the purposes of read across to hexyl salicylate