Butyl glycollate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-04-07 to 2000-06-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Principles of method if other than guideline:

The purpose of this study was twofold. The primary purpose was to determine a 4-hour inhalation approximate lethal concentration (ALC) of H-24386 (butyl glycollate or Polysolvan O) in male rats. The ALC is defined as the lowest atmospheric concentration tested which caused the death of 1 or more exposed rats either on the day of exposure or within at least 14 days following exposure. The secondary purpose was to evaluate the potential of the test substance to induce lesions in the nose, pharynx/larynx, and lungs following a single 4-hour inhalation exposure.

GLP compliance:

not specified

Test type:

other: Approximate lethal concentration (ALC) determination

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butyl glycollate

EC Number:

230-991-7

EC Name:

Butyl glycollate

Cas Number:

7397-62-8

Molecular formula:

C6H12O3

IUPAC Name:

butyl glycolate

Constituent 2

Reference substance name:

Polysolvan O

IUPAC Name:

Polysolvan O

Constituent 3

Reference substance name:

Glycolic acid-n-butyl ester

IUPAC Name:

Glycolic acid-n-butyl ester

Details on test material:

- Name of test material (as cited in study report): H-24386 (butyl glycollate or Polysolvan O)
- Physical state: Light tan liquid
- Analytical purity: 99.07%
- Impurities (identity and concentrations): 0.21% butanol, 0.70% unknown, 0.04% water
- Composition of test material, percentage of components: 99.07% n-butyl glycolate, 0.21% butanol, 0.70% unknown, 0.04% water
- Stability under test conditions: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed.

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina, USA
- Age at study initiation: about 8 - 9 weeks
- Weight at study initiation: 230 - 308 g
- Fasting period before study: no
- Housing: either singly or in pairs in suspended, stainless steel, wire-mesh cages
- Diet (e.g. ad libitum): Except during exposure, PMI Nutrition International, Inc. Certified Rodent LabDiet® 5002, ad libitum.
- Water (e.g. ad libitum): tap water from United Water Delaware, ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 1 °C
- Humidity (%): 50 ± 10%.
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2000-04-12 To: 2000-05-19

Administration / exposure

Route of administration:

other: vapor or aerosol/vapor

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The exposure chamber was constructed of glass (cylindrical) . A polycarbonate baffle inside the exposure chamber promoted uniform chamber distribution of the test atmosphere
- Exposure chamber volume: 34 L
- Method of holding animals in test chamber: During exposure, rats were individually restrained in perforated stainless steel cylinders with conical nose pieces. The restrainers were inserted into the polymethylmethacrylate faceplate of the exposure chamber so that only the nose of each rat extended into the chamber
- System of generating particulates/aerosols: Chamber atmospheres of 3.0, 4.3, or 6.2 mg/L H-24386 consisted of a mixture of aerosol and vapor. Aerosol/vapor atmospheres were generated by atomization of H-24386 in air with a Spraying Systems nebulizer. The test substance was metered into the nebulizer with a Cole Palmer Masterflex® Console Drive pump. Filtered high-pressure air introduced at the nebulizer atomized the test substance and carried the resulting atmosphere into the exposure chamber. Chamber concentrations of H-24386 were controlled by varying the test substance feed rate to the nebulizer.
At a chamber concentration of 0.40 mg/L, the atmosphere consisted of vapor only. Vapor atmospheres of H-24386 were generated by metering the liquid test substance into a heated, glass flask with a Harvard Apparatus model 22 Compact Infusion pump. Filtered, high-pressure air introduced into the flask carried the resulting atmosphere into the exposure chamber. Chamber concentrations of H-24386 were controlled by varying the test substance feed rate to the flask.
- Method of particle size determination: Sierra® Series 210 Cyclone Preseparator/Cascade Impactor and Sierra® Series 110 Constant Flow Air Sampler
- Treatment of exhaust air: test atmospheres were exhausted through a dry-ice cold trap followed by a MSA charcoal/HEPA filter cartridge prior to discharge into the fume hood
- Temperature, humidity, pressure in air chamber: . Chamber temperature: 22 ± 2°C. Chamber relative humidity: 50 ± 10% measured with an Omega model RH5100C Digital Psychrometer and recorded 4 times during each exposure. Chamber oxygen concentration: at least 19% measured with a Biosystems model 3100R Oxygen Analyzer and recorded 4 times during each exposure

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric analysis and gas chromatography for the aerosol and vapor components. The aerosol concentration was calculated from the difference in the pre- and post-sampling filter weights divided by the volume of chamber atmosphere sampled.
For the atmospheric vapor concentration, aliquots of impinger solutions were injected into a Hewlett Packard model 5890 Series II Gas Chromatograph equipped with a flame ionization detector. All samples were chromatographed isothermally at 45°C on a 60 meter Restek RTX1 column.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
3.8 to 5.5% less than 1 µm,
49 to 54% less than 3 µm
96 to 98% less than 10 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
MMAD: 2.8 to 3.1 µm

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.4, 3.0, 4.3, 6.2 mg/L (concentrations of 3.0 mg/L and above consisted of a mixture of aerosol and vapor, at 0.40 mg/L, chamber atmospheres consisted of vapor only).

No. of animals per sex per dose:

Main group: 6
Satellite group: 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Six rats per group were designated for ALC determination. These rats were observed for mortality and clinical signs of toxicity during each exposure and immediately after they were removed from the restrainers following exposure. During a 14-day post exposure period, all rats designated for ALC determination were observed each day for mortality, and were weighed and observed for clinical signs of toxicity 1 to 4 times per week. At the end of the recovery period, all rats designated for ALC determination were sacrificed by carbon dioxide asphyxiation and discarded without pathological evaluation.

The remaining 5 rats per group were designated as satellite animals, approximately 24 hours following exposure these rats were sacrificed by carbon dioxide anesthesia and exsanguination. These rats were given a complete gross examination and representative samples of the nose, pharynx/larynx, and lungs were saved at necropsy. All tissues were fixed in 10% neutral buffered formalin. All tissues were processed, embedded in paraffin, cut at a nominal thickness of 5 micrometers, stained with hematoxylin and eosin (H&E), and examined microscopically.
These rats were not observed for clinical signs of toxicity during or after exposure nor during the 24-hour period prior to sacrifice. No body weight determinations were done on these animals
- Necropsy of survivors performed: yes

Statistics:

Generally calculation of means ± standard deviation.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

other: approximate lethal concentration (ALC)

Effect level:

> 6.2 mg/L air (nominal)

Mortality:

No deaths occurred.

Clinical signs:

other: No clinical signs of toxicity attributable to the test item exposure were observed during the study.

Body weight:

All rats exposed at 3.0 mg/L and above and 4 of 6 rats exposed at 0.40 mg/L experienced slight to severe body weight losses the day after exposure. Weight losses ranged from 0.2 to 14.3 percent of initial body weight. All rats subsequently resumed normal weight gains and gained weight for the remainder of the recovery period.

Gross pathology:

There were no gross abnormalities detected. Compound-related microscopic findings consistent with tissue irritation were present in the nose of rats exposed at concentrations of 3.0 mg/L and above. There were no compound-related microscopic findings in the pharynx/larynx and lungs.

Any other information on results incl. tables

Exposure chamber vapor and aerosol characterization:

Aerosol concentration (mg/L)	Aerosol size			Vapor concentration (mg/L)
Mean (range)	MMAD (µM)	GSD	Percent <10 µm	Mean (range)
0	-*	-*	-*	0.40 (0.35-0.48)
2.3 (1.4-2.8)	2.8	1.8	98%	0.7 (0.021-1.5)
3.1 (2.2-4.1)	3.1	2.0	96%	1.2 (1.1-1.3)
5.2 (3.9-7.5)	3.1	1.9	97%	1.1 (0.95-1.2)
* exposure consisted of vapor only, MMAD = Mass Median Aerodynamic Diameter, GSD = geometric standard deviation,

 

 

Exposure chamber concentration and mortality:

Total concentration (mg/L)	Mortality
Mean (range)	Deaths/exposed
0.40 (0.35-0.48)	0/6
3.0 (1.4-4.2)	0/6
4.3 (3.4-5.3)	0/6
6.2 (5.0-8.6)	0/6

 

Mean body weight (g)

	0.4 mg/L	3.0 mg/L	4.3 mg/L	6.2 mg/L
Day 0	254.2	242.8	297.3	238.3
Day 1	249.7	235.9	272.5	225.0
Day 2	260.2	247.8	285.6	237.1
Day 7	303.0	294.2	323.5	Not measured
Day 14	344.6	350.3	365.1	327.2

 

Summary of clinical findings

	0.4 mg/L	3.0 mg/L	4.3 mg/L	6.2 mg/L
Scab	0	0	1	0
Discharge (left eye)	0	1	0	0
Discharge (wound hindpaw)	0	1	0	0
Swollen hind paw	0	1	0	0

 

Incidence of gross observation

	0.4 mg/L	3.0 mg/L	4.3 mg/L	6.2 mg/L
Pharynx/larynx	NAD	NAD	NAD	NAD
Lungs	NAD	NAD	NAD	NAD
Nose	NAD	NAD	NAD	NAD
NAD = no abnormality detected

Incidence of microscopic lesions

	0.4 mg/L	3.0 mg/L	4.3 mg/L	6.2 mg/L
Lungs: NAD	-	-	-	5/5
Pharynx/larynx: inflammation	-	-	-	1/5
Nose level I/II NAD Degeneration/regeneration Inflammation Squamous metaplasia Olfactory necrosis	5/5	2/5 2/5   5/5	5/5 2/5   5/5	5/5 4/5   5/5
Nose level III/IV NAD Degeneration/regeneration Inflammation Olfactory necrosis	5/5	1/5     4/5	1/5   5/5	2/5 1/5 5/5
NAD = no abnormality detected

 

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On an acute inhalation basis, H-24386 (butyl glycollate or Polysolvan O) is considered to be of very low toxicity (ALC > 2.0 mg/L).