Methyl 3-mercaptopropionate

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983-04-14 to 1983-06-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study performed with methods not supported by an established guideline. However, the study provided detailed information on materials, methods and results. The study did however fail to provide complete information on the test substance (i.e. purity) and different animals were not used for each dose level.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The purpose of the study was to evaluate the potential respiratory irritation of the test substance in treated mice. The basic method was developed by Y. Alarie (Arch. Environ. Health, 13:433-449, 1966).

GLP compliance:

yes

Type of method:

in vivo

Endpoint addressed:

respiratory irritation

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 3-mercaptopropionate

EC Number:

220-912-4

EC Name:

Methyl 3-mercaptopropionate

Cas Number:

2935-90-2

Molecular formula:

C4H8O2S

IUPAC Name:

methyl 3-sulfanylpropanoate

Details on test material:

- Name of test material (as cited in study report): methyl mercaptopropionate
- Molecular formula (if other than submission substance): N/A
- Molecular weight (if other than submission substance): N/A
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): N/A
- Substance type: active
- Physical state: liquid

Test animals

Species:

mouse

Strain:

other: outbred SPF (CD-1, COBS)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc.
- Age at study initiation: young adults
- Weight at study initiation: 20-25 g
- Fasting period before study: N/A
- Housing: Animals were group housed in stainless-steel wire-mesh cages.
- Diet (e.g. ad libitum): Purina Lab Chow #5001 was available ad libitum except during exposures.
- Water (e.g. ad libitum): Tap water was available ad libitum except during exposures.
- Acclimation period: 7 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Every attempt was made to maintain temperatures at 70 +/- 4 degrees F.
- Humidity (%): Every attempt was made to maintain a relative humidity of 40-60%
- Air changes (per hr): N/A
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: N/A To: N/A

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

air

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The exposure apparatus was a head only plastic exposure chamber with attached plethysmographes and a volume of approximately 750 mls. The test substance was generated as a vapor. In no case was the oxygen concentration allowed to fall below 19% within the chambers. The vapors were generated by use of a water jacketed counter-flow column maintained at approximately 80 degrees F. The test substance was metered into the top of the column with air introduced through the bottom.
- Method of holding animals in test chamber: Animals were exposed in a specially designed head only exposure chamber. Each mouse was placed in a plethysmograph with its head projecting into the plastic exposure core.
- Source and rate of air: Airflow was maintained at 7.5 liters/minute.
- Method of conditioning air: N/A
- System of generating particulates/aerosols: N/A
- Temperature, humidity, pressure in air chamber: N/A
- Air flow rate: Airflow was maintained at 7.5 liters/minute (Chamber equilibration time T99 (theoretical)=0.5 minutes).
- Air change rate: N/A
- Method of particle size determination: N/A
- Treatment of exhaust air: The vapors were exhausted from an alternate outlet at the column top and directed into the air input opening of the chamber.
TEST ATMOSPHERE
- Brief description of analytical method used: Concentrations were analytically verified using THC.
- Samples taken from breathing zone: N/A

VEHICLE (if applicable)
- Justification for use and choice of vehicle: N/A
- Composition of vehicle: air
- Type and concentration of dispersant aid (if powder): N/A
- Concentration of test material in vehicle: N/A
- Lot/batch no. of vehicle (if required): N/A
- Purity of vehicle: N/A

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The dose levels were analytically verified using THC.
The following mean analytical concentrations were determined: 807.50 +/-31.82 ppm, 283 ppm, 460 +/-7.07 ppm, 365 +/-28.28 ppm and 435.5 +/-9.19 ppm for the nominal concentrations of 4.75, 1.19, 2.21, 1.63, and 1.81 mg/L, respectively..

Duration of treatment / exposure:

1 minute per exposure

Frequency of treatment:

The animals were exposed first to the test substance for one minute, next to room air for ten minutes, and to a second one minute exposure to the test substance. The respiratory patterns of the animals were continuously monitored.

Post exposure period:

Following the second exposure, animals were monitored for a minimum of 5 minutes or until recovery while breathing room air.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
4.75, 1.19, 2.21, 1.63 and 1.81 mg/L
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
807.50 +/-31.82, 283, 460 +/-7.07, 365 +/-28.28 and 435.5 +/-9.19 ppm, respectively for the nominal concentrations listed above
Basis:
analytical conc.

No. of animals per sex per dose:

Two tests were performed (Test A and B). Four animals were included in each test and each animal was exposed to each dose level with a recovery period between doses.

Control animals:

other: A control respiratory pattern was established during which the animals used for treatment were first exposed to room air.

Details on study design:

N/A

Examinations

Examinations:

An evaluation of the plethysographic respiratory response elicited at the various concentration levels of the test substance was performed. The responses were utilized to develop a concentration response relationship by plotting the group mean change in respiratory rate vs. the logarithm of the concentration level of the test substance. Where possible, the RD MDL with confidence limits was determined using the Finney's Probit Analysis.

Positive control:

none

Results and discussion

Details on results:

The results of the study indicated that exposure to the test substance at nominal concentrations of 1.63-4.75 mg/L in air resulted in slight to moderate depressions in respiratory rates with inconsistent indications across these groups of slight to moderate upper respiratory irritation. The data further suggested that no upper respiratory irritation was produced in the mice exposed to the test substance at a nominal concentration of 1.19 mg/L in air.

Any other information on results incl. tables

Results: Rated change in respiratory rate from previous 1 minute
		4.75 mg/L	1.19 mg/L	2.21 mg/L	1.63 mg/L	1.81 mg/L	Key: 0=unchanged or increased 1=0-25% increase 2=25-50% increase 3=50% or greater increase
Test A	Mouse 1	0	1	0	0	0
	Mouse 2	0	0	0	0	1
	Mouse 3	3b	0	3a	1	2d
	Mouse 4	2a	0	2d	0	1
	Mean (% change)	-6.2%	8.0%	-17.2%	2.1%	-7.9%
Test B	Mouse 1	2d	1	0	1	1
	Mouse 2	1	0	1	0	0
	Mouse 3	3b	0	1	2c	1
	Mouse 4	2a	1	1	1	1
	Mean (% change)	-37.6%	1.4%	-6.9%	-9.4%	-6.3%

a=Recorded respiratory pattern indicated moderate-severe respiratory pauses.

b=Recorded respiratory pattern indicated severe respiratory pauses.

c=Recorded respiratory pattern indicated moderate respiratory pauses.

d=Recorded respiratory pattern indicated slight respiratory pauses.

Applicant's summary and conclusion

Conclusions:

The test substance was evaluated for respiratory irritancy in mice. The results of the study indicated that exposure to the test substance at nominal concentrations of 1.63-4.75 mg/L in air resulted in slight to moderate depressions in respiratory rates with inconsistent indications across these groups of slight to moderate upper respiratory irritation. The data further suggested that no upper respiratory irritation was produced in the mice exposed to the test substance at a nominal concentration of 1.19 mg/L in air.

Executive summary:

N/A