Isooctyl mercaptoacetate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Materials and methods

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isooctyl mercaptoacetate

EC Number:

246-613-9

EC Name:

Isooctyl mercaptoacetate

Cas Number:

25103-09-7

Molecular formula:

C10H20O2S

IUPAC Name:

2-methylheptyl 2-sulfanylacetate

Details on test material:

Identification: Isooctyl thioglycolate (IOTG)
CAS no. 25103-09-7
Purity >98%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Groups of 10 male and 10 female rats were exposed to 0, 1.6 or 3.2 ppm IOTG vapor for 6 hours/day, 5 days/week for 10 exposures.  Vapors of IOTG were generated by counter-current exchange between air and liquid IOTG at room temperature in a 15-plate perforated plate distillation column. 
Feed and water were removed during the exposure period (including controls) but were available ad libitum at all other times.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Analytical concentrations of IOTG vapor in the exposure chambers were determined by gas chromatography.

Duration of treatment / exposure:

2 weeks

Frequency of treatment:

6 hrs/day, 5 days/week (10 exposures)

Doses / concentrations

Remarks:

Doses / Concentrations:
1.6 or 3.2 ppm (0.19 or 0.38 mg/m3)
Basis:

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

Post-exposure period: none

Examinations

Observations and examinations performed and frequency:

All animals were weighed on exposure days 0, 3, 6, 8 and 10.  The rats were observed during each exposure day for signs of toxicity and changes in appearance and demeanor.  After 9 days of exposure, basic hematology and urinalysis studies were conducted on 7 rats/sex/group.  Hematological parameters included red blood cell counts, total and differential white blood cell counts, hemoglobin concentrations and packed cell volume.  Blood for hematology was obtained from the tail veins.  Urinalysis included the determination of pH, specific gravity, glucose, ketones, bilirubin, occult blood, urobilinogen and protein in the urine.  At necropsy, clincial chemistry determinations of blood urea nitrogen (BUN), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphatase, and serum glucose levels were done on 7 rats/sex/group.  Blood for clinical chemistry tests were obtained from the cervical vessels.  

Sacrifice and pathology:

Gross necropsy was conducted on all rats.  Prior to necropsy, the rats were fasted overnight, weighed, anesthetized with methoxyfluorane to facilitate the clamping of the trachea, and than killed by decapitation.  The lungs and trachea were removed as a unit and expanded by a hand syringe with 10% formalin.  Body weights and organ weights for liver, kidneys, brain, heart thymus and testes were obtained from all rats at necropsy.  Organs to body weight ratios were calculated.  Histopathology was not performed on any of the treated animals.

Statistics:

Hematology, urinalysis, clinical chemistry, organ and body weight data were analyzed using an analysis of variance and Dunnett's test (Steela nd Torrie, 1960.)  The level of significance in all cases was p<0.05.

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 examined

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:

not examined

Histopathological findings: neoplastic:

not examined

Effect levels

Dose descriptor:

NOAEL

Effect level:

3.2 ppm

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Mean analytical concentrations for the 10 exposures were 1.6
(SD = 0.6) ppm and 3.2 (SD = 2.3) ppm.  No clinical signs of
irritation or toxicity were seen in any exposed male or
female rats throughout the study.  All male and female
exposed rats had weight gain comparable to male and female
control rats.  There were no exposure-related effects on
hematology, urinalysis, clinical chemistry, organ and
terminal body weights for male and female rats.  There were
no exposure-related lesions observed in any rats at
necropsy.  Histopathology was not performed on any of the
treated animals.

Applicant's summary and conclusion

Executive summary:

Groups of 10 Sprague-Dawley rats/sex were exposed to 0, 1.6 or 3.2 ppm (0, 0.19 or 0.38 mg/m³) IOTG vapor for 6 hours/day, 5 days/week for 10 exposures (Yakel and Kociba, 1979). Vapors of IOTG were generated by counter-current exchange between air and liquid IOTG at room temperature in a 15-plate perforated plate distillation column. Analytical concentrations of IOTG vapor in the exposure chambers were determined by gas chromatography. All animals were weighed on exposure days 0, 3, 6, 8 and 10. The rats were observed during each exposure day for signs of toxicity and changes in appearance and demeanor. After 9 days of exposure, basic hematology and urinalysis studies were conducted on 7 rats/sex/group. At necropsy, clinical chemistry determinations were performed on 7 rats/sex/group. Gross necropsy was conducted on all rats. Body weights and organ weights were obtained from all rats at necropsy. Histopathology was not performed on any of the treated animals. Mean analytical concentrations for the 10 exposures were 1.6 (SD = 0.6) ppm and 3.2 (SD = 2.3) ppm. No clinical signs of irritation or toxicity were seen in any exposed rats throughout the study. All exposed rats had weight gain comparable to control rats. There were no exposure-related effects on hematology, urinalysis, clinical chemistry, organ and terminal body weights for male and female rats. There were no exposure-related lesions observed in any rats at necropsy. The NOAEL was 3.2 ppm.