2-methylbutane

Endpoint summary

Description of key information

Acute Toxicity - Oral LD₅₀ > 2000 mg/Kg in rats (OECD TG 401)

Acute Toxicity - Inhalation LC₅₀ > 25300 mg/m³ (OECD TG 403)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restriction because it is in compliance with OECD principles of GLP and E.U. Council Decision on GLP.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: Crl:CDBR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc.
- Age at study initiation: 8 to 9 weeks old
- Weight at study initiation: Males: 206 to 221 grams; Females: 206 to 213 grams
- Fasting period before study: overnight
- Housing: individually housed in suspended stainless steel and wire mesh cages with absorbent paper below cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68 to 76 °F
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

IN-LIFE DATES: From: 1996-08-07 To: 1996-08-21

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 3.33 ml/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed once or twice a day and body weights were obtained on the day prior to testing, the day of dosing, and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

None were performed.

Preliminary study:

No preliminary study was performed and the limit dose was used.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

One animal died within an hour of dosing due to intubation error. No deaths were associated with oral administration of the test material.

Clinical signs:

other: Clinical signs were observed in all of the remaining animals. The clinical signs including oral or nasal discharge, swollen abdomen, anogenital staining, and or soft or mucoidal stools were transient and limited to the day of exposure.

Gross pathology:

There were no gross abnormalities observed during necropsy.

Interpretation of results:

other: Not classified

Remarks:

Not classified because LD50 is greater than the requirements for a Category 4 toxicant (2000 mg/kg) Criteria used for interpretation of results: EU

Conclusions:

The results indictae that n-pentane is not acutely toxic via the oral route of exposure.

Executive summary:

In an acute oral toxicity study, 5 rats per sex were given a single oral dose of undiluted n-pentane (pure) at a dose of 2000 mg/kg (3.33 ml/kg) and were observed for 14 days. There were no mortalities or consistent signs of systemic toxicity through the 14 days with no abnormalities noted at necropsy. The estimated LD50 for n-pentane is thus greater than 2000 mg/kg. This study is classified as reliable without restrictions because it is in compliance with OECD principles of GLP and E.U. Council Decision on GLP and follows the appropriate test guidelines

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable with restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the study adhered to the principles outlines in OECD 423 guidelines.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

Only summary information was provided. Key study information (purity, stability, characterization, and verification of the test material; strain, selection, diet, and housing of animals) was not provided.

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not reported

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: none provided

Doses:

5000 mg/kg

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed daily and weighedat study initiation, on day 7, and on day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight

Statistics:

none

Preliminary study:

not reported

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No animals died over the 14 days of observation.

Clinical signs:

other: Clinical signs observed over the first 24 hours after exposure included depression (sometimes slight), red stains on the nose and/or eyes, rough coat, soft feces, a hunched appearance, and urine stains. All animals appeared normal from day 2 until study

Gross pathology:

There were no gross abnormalities observed.

Interpretation of results:

other: Not classified

Remarks:

Not classified because LD50 is greater than the requirements for a Category 4 toxicant (2000 mg/kg) Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 for cyclopentane is greater than 5000 mg/kg.

Executive summary:

In an acute oral toxicity study, cyclopentane was administered orally as a single 5000 mg/kg dose to male and female rats. Specifics of the treatment and vehicle were not provided. Animals were observed for 14 days, then a gross necropsy was performed. In the first 24 hours, rats exhibited depression or slight depression, red stains on the nose and/or eyes, rough coat, soft feces, hunched appearance, and urine stains. All animals were normal by day 2. No mortalities occurred during treatment or throughout the 14 -day observation period. There were no treatment-related changes in body weight or gross pathology. Based on the results, the oral LD50 of cyclopentane in male and female rats is greater than 5000 mg/kg.

This study received a Kilmisch score of 2 and is classified as reliable with restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the study adhered to the principles outlines in OECD 423 guidelines.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Two key read across studies from structural analogues available for assessment.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable with restrictions because there are no statements indicating if the study was conducted according to GLPs or other accepted guidelines, and the endpoint measured was not mortality.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

no guideline available

Principles of method if other than guideline:

The effect of acute inhalation exposure to the test substance on neurobehaviour, specifically the shortening of the duration of maximal tonic extension in male rats and the slowing of the development of tonic extension in female mice, was examined. Rats or mice were exposed to the test substance, then exposed to an electrical impulse. The effect of the exposure on the reaction to the impulse was measured.

GLP compliance:

not specified

Test type:

other: acute inhalation neurotropic effects

Limit test:

no

Species:

other: rat (males) and mouse (females)

Strain:

other: Wistar albino and H

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: Males: 0.5 to 1 year; Females: 2 to 4 months
- Weight at study initiation: Males: mean of 350 g; Females: not reported
- Housing: Males: 4 per cage; Females: 16 per cage
- Diet (e.g. ad libitum): Males: 12 grams per day; Females: ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Climatized
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass chamber, diffusion tubes used for stabilization of air concentration
- Exposure chamber volume: 80 litre
- Method of holding animals in test chamber: animals placed in small plastic boxes
- Temperature, humidity, pressure in air chamber: dynamic conditions

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gas chromatography

Duration of exposure:

h

Remarks on duration:

4 hours for male rats and 2 hours for female mice

Concentrations:

3 concentrations, not reported

No. of animals per sex per dose:

Males: 4; Females: 8 (see details below)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: animals were used for multiple experiments, and were observed accordingly
- Frequency of observations and weighing: not reported
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Statistics:

All data were analyzed using linear regression analysis.

Key result

Sex:

male

Dose descriptor:

other: Isoeffective air concentration

Effect level:

21 000 ppm

Exp. duration:

4 h

Remarks on result:

other: 90% CL: 3200 ppm; calculated as the concentration resulting in in 37% depression of the critical effect level (i.e., shortening of the tonic extension of hindlimbs by 3 seconds)

Key result

Sex:

female

Dose descriptor:

other: Isoeffective air concentration

Effect level:

23 500 ppm

Exp. duration:

2 h

Remarks on result:

other: 90% CL: 6800 ppm; calculated as the concentration resulting in in 30% depression of the critical effect level (i.e., lengthening of the latency of extension by 0.6 seconds)

Mortality:

No mortality reported

Clinical signs:

other: Not reported

Body weight:

Not reported

Gross pathology:

Not reported

Other findings:

None reported

Interpretation of results:

other: Not classified

Remarks:

Not classified because LC50 is greater than the requirements for a Category 4 vapour toxicant (20 mg/L) Criteria used for interpretation of results: EU

Conclusions:

No mortality was seen at exposures > 20,000 ppm for either rats or mice, so the test substance is not classified under the EU classification scheme.

Executive summary:

In an acute inhalation toxicity study, groups of young adult male Wistar strain albino rats (4 per dose level) and female H strain mice (8 per dose level) were exposed by inhalation route to n-pentane for 4 hours (males) or 2 hours (females) to whole body at 3 concentrations. 

 

Animals were examined for neurotropic effects, specifically depression of seizure responses after exposure to an electrical impulse. Mortality was not reported, and no long-term systemic effects were reported. No NOAEL was reported, and the LC50 was not calculated. The concentration resulting in 37% depression of the shortening of the tonic extension of hindlimbs by 3 seconds in male rats was found to be 21000 ppm, while the concentration resulting in 30% depression of the lengthening of the latency of extension by 0.6 seconds in mice was found to be 23500 ppm.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because there are no statements indicating if the study was conducted according to GLPs or other accepted guidelines, and the endpoint measured was not mortality.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1992-11-18 to 1992-12-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study is classified as reliable without restrictions because it is in compliance with international guidelines for acute inhalation toxicity studies.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, UK Limited
- Age at study initiation: male: 6 weeks; female: 8 weeks
- Weight at study initiation: ~200 grams
- Fasting period before study: not reported
- Housing: Stainless steel cages (size 35 cm x 53 cm x 25 cm height) suspended on a movable rack
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24⁰C
- Humidity (%): 27 to 65%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light):not reported

IN-LIFE DATES: From: 1992-11-18 To: 1992-12-10

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: Air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: square perspex chambers with pyramidal tops attached to a vapour generator placed in a water bath maintained at 30 degrees celcius
- Exposure chamber volume: 120 Litres
- Method of holding animals in test chamber: wire mesh partitions to hold 10 animals at a time
- Source and rate of air: dried, filtered, oil free air supplied at 25 litres per minute
- Method of conditioning air: not reported
- System of generating particulates/aerosols: atomiser with PTFE tubing fitted with a syringe pump
- Method of particle size determination: not reported
- Treatment of exhaust air: exhaust to atmosphere through a carbon scrubbing system
- Temperature, humidity, pressure in air chamber: 23 to 24 degrees celcius, humidity and pressure not reported

TEST ATMOSPHERE
- Brief description of analytical method used: 5 samples were drawn through a gas absorption trap containing acetone chilled to -70⁰C. Samples were diluted with methanol and then 3µL aliquots of sample solution were inject onto a Gas Chromatography column. Concentration of cylcopentane was calculated using expression:
Cx = (Ax - I)/S where:
Cx = Concentrationof cyclopentane in aliquot (mg/mL)
Ax = Peak area due to cyclopentane
S = Gradient of standard curve
I = Intercept of standard curve
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable):25.30 mg/L
- Justification of choice of vehicle: not reported
- Lot/batch no. (if required): not reported
- Purity: not reported

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:not reported
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not reported

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: not provided

Analytical verification of test atmosphere concentrations:

yes

Remarks:

25.30 ± 0.76 mg/L

Duration of exposure:

ca. 4 h

Concentrations:

25.30 mg/L (26.4 mg/L - nominal concentration)

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs monitored at 0.25, 0.50, 1.0 hours and then hourly during exposure and once daily during the 14-day post-expsoure observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, food and water consumption

Statistics:

Mean and standard deviation (SD) computed for body weight, concentration analysis, food and water consumption, and lung to body weight ratios.

Preliminary study:

The 4-hour inhalation LC50 of cyclopentane is >25.3 mg/L.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 25.3 mg/L air

Exp. duration:

4 h

Mortality:

No deaths were observed.

Clinical signs:

other: Hunched posture was observed in all rats (male and female) during hours 1 to 4 of the expsoure period.

Body weight:

A few male rats exhibited reduction in bodyweight gain on the day following exposure. Subsequently though, bodyweight gain was similar to that observed in control rats. One male rat also exhibited wet fur around the snout and jaws immediately following exposure period.

Gross pathology:

No macroscopic abnormalities were noted in rats exposed to cyclopentane and individual findings such as basophilic cortical tubules in kidneys, macophage aggregates, alveolar hemorrhage and pneumonitis in the lungs were considered spontaneous in origin and not treatment-related.

Other findings:

- Organ weights: Lung to body-weight ratios were found to be within normal limits for all male and female rats.
- Other observations: Food consumption was found to be slightly reduced in male rats for a single day while water consumption seemed unaffected following exposure to cyclopentane.

Table 1. Clinical signs during observation period

Group	Signs	Number of animals showing sings
		Day of observation period post-exposure
		0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Control Males	Normal behaviour and appearance	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
Control Females	Normal behaviour and appearance	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5
Males (25.3 mg/L)	Normal behaviour and appearance	4	5	5	5	5	5	5	5	5	5	5	5	5	5	5
	Wet fur around snout and jaws	1
Females (25.3 mg/L)	Normal behaviour and appearance	5	5	5	5	5	5	5	5	5	5	5	5	5	5	5

Table 2. Mean body weight during study period.

Group	Day of Observation and Mean weight in grams
	-5	-4	-3	-2	-1	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Male Control	175	185	194	201	207	213	221	230	239	248	257	264	272	278	283	288	298	303	308	315
Female Control	189	195	202	207	211	214	216	220	220	225	227	233	231	238	235	238	239	246	248	251
Male (25.3 mg/L)	177	183	194	202	208	217	233	231	238	248	256	265	271	279	284	291	299	305	309	316
Female (25.3 mg/L)	189	191	198	202	201	205	208	214	215	218	223	227	226	228	232	234	236	240	247	248

Rats exposed at Day 0. Bodyweight recorded before exposure.

Table 3. Microscopic pathology incidence summary.

	Control Males	Males (25.3 mg/L)	Control Females	Females (25.3 mg/L)
Animals on study	5	5	5	5
Animals completed	5	5	5	5
Lungs
Examined	5	5	5	5
No abnormalities detected	2	2	3	4
Penumonitis (Total)	0	0	0	1
Minimal	0	0	0	1
Alveolar collapse	1	0	0	0
Moderate	1	0	0	0
Macrophage aggregates (Total)	2	3	0	0
Minimal	2	2	0	0
Bronchiolar associated lymphoid tissue (Total)	1	0	0	0
Moderate	1	0	0	0
Recent alveolar haemorrhage (Total)	0	1	2	0
Minimal	0	1	2	0
Liver
Examined	5	5	5	5
No abnormalities detected	5	5	5	5
Kidneys
Examined	5	5	5	5
No abnormalities detected	1	1	4	3
Basophilic cortical tubules (Total)	4	4	1	2
Minimal	4	4	1	2

Interpretation of results:

other: Not classified

Remarks:

Not classified because LC50 is greater than the requirements for a Category 4 vapour toxicant (20 mg/L) Criteria used for interpretation of results: EU

Conclusions:

4-hour acute inhalation toxicity LC50 >25.3 mg/litre

Executive summary:

In an acute inhalation toxicity study, 5 albino Sprague-Dawley rats/sex were administered 25.30 mg/L (nominal concentration of 26.40 mg/L) of cyclopentane via the inhalation route (whole body exposure) for a period of 4 hours. The rats were observed constantly for signs of reaction during the exposure period and twice daily during the 14-day observation period that followed. Clinical signs were recorded at the end of chamber equilibration period, at 0.25, 0.50, and 1 hours and then at hourly intervals during the exposure period. Clinical signs were recorded once in the morning and then as necessary through the observation period. Bodyweight, food, and water consumption determinations were made daily. At termination, rats were killed and subjected to a detailed macroscopic examination. The liver and kidneys of each rat were evaluated histopathologically under light microscope.

There were no observed mortalities and hunched posture was observed in all rats (male and female) during hours 1 to 4 of the exposure period. A few male rats exhibited reduction in bodyweight gain on the day following exposure. Subsequently though, bodyweight gain was similar to that observed in control rats. Food consumption was found to be slightly reduced in male rats for a single day while water consumption seemed unaffected following exposure to cyclopentane. One male rat also exhibited wet fur around the snout and jaws immediately following the exposure period.

No macroscopic abnormalities were noted in rats exposed to cyclopentane and individual findings such as basophilic cortical tubules in kidneys, macophage aggregates, alveolar hemorrhage and pneumonitis in the lungs were considered spontaneous in origin and not treatment-related. Lung to body-weight ratios were found to be within normal limits for all male and female rats.

Based on the results discussed above, the 4-hour inhalation LC₅₀ for cyclopentane is >25.30 mg/L. Cyclopentane is practically non-toxic in the acute inhalation toxicity test in rats. This study received a Kilmisch score of 1 and is classified as reliable without restrictions because it is in compliance with international guidelines for acute.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 25 300 mg/m³ air

Physical form:

inhalation: vapour

Quality of whole database:

Two key read across studies from structural analogues and 1 supporting substance specific study available for assessment.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Only supporting inhalation toxicity data is available for 2-methylbutane. However, key oral and inhalation toxicity data is available for structural analogues, pentane and cyclopentane and presented in the dossier. This data is read across to 2-methylbutane based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Acute Oral Toxicity

 

Pentane

 

In a key acute oral toxicity study (ExxonMobil, 1996), 5 rats per sex were given a single oral dose of undiluted test material (n-pentane (pure)) at a dose of 2000 mg/Kg (3.33 mL/Kg) and were observed for 14 days. There were no mortalities or consistent signs of systemic toxicity through the 14 days with no abnormalities noted at necropsy. The estimated LD₅₀ for n-pentane is thus greater than 2000 mg/Kg. This study is classified as reliable without restrictions because it is in compliance with OECD principles of GLP and E.U. Council Decision on GLP and follows the appropriate test guidelines.

 

Cyclopentane

 

In a second key acute oral toxicity study (Phillips Petroleum Company, 1982), the test material (cyclopentane) was administered orally as a single 5000 mg/Kg dose to male and female rats. Specifics of the treatment and vehicle were not provided. Animals were observed for 14 days, then a gross necropsy was performed. In the first 24 hours, rats exhibited depression or slight depression, red stains on the nose and/or eyes, rough coat, soft feces, hunched appearance, and urine stains. All animals were normal by day 2. No mortalities occurred during treatment or throughout the 14 -day observation period. There were no treatment-related changes in body weight or gross pathology. Based on the results, the oral LD₅₀ of cyclopentane in male and female rats was determined to be greater than 5000 mg/Kg.

Acute Inhalation Toxicity

 

Pentane

 

In a key acute inhalation toxicity study (Frantik et al., 1994), groups of young adult male Wistar strain albino rats (4 per dose level) and female H strain mice (8 per dose level) were exposed by inhalation route to the test material (n-pentane) for 4 hours (males) or 2 hours (females) to whole body at 3 concentrations. 

 

Animals were examined for neurotropic effects, specifically depression of seizure responses after exposure to an electrical impulse. Mortality was not reported, and no long-term systemic effects were reported. No NOAEL was reported, and the LC₅₀was not calculated. The concentration resulting in 37% depression of the shortening of the tonic extension of hindlimbs by 3 seconds in male rats was found to be 21000 ppm, while the concentration resulting in 30% depression of the lengthening of the latency of extension by 0.6 seconds in mice was found to be 23500 ppm.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because there are no statements indicating if the study was conducted according to GLPs or other accepted guidelines, and the endpoint measured was not mortality.

 

Cyclopentane

 

In a second acute inhalation toxicity study (Shell, 1993), 5 albino Sprague-Dawley rats/sex were administered 25.30 mg/L (nominal concentration of 26.40 mg/L) of the test material (cyclopentane) via the inhalation route (whole body exposure) for a period of 4 hours. The rats were observed constantly for signs of reaction during the exposure period and twice daily during the 14-day observation period that followed. Clinical signs were recorded at the end of chamber equilibration period, at 0.25, 0.50, and 1 hours and then at hourly intervals during the exposure period. Clinical signs were recorded once in the morning and then as necessary through the observation period. Bodyweight, food, and water consumption determinations were made daily. At termination, rats were killed and subjected to a detailed macroscopic examination. The liver and kidneys of each rat were evaluated histopathologically under light microscope.

 

There were no observed mortalities and hunched posture was observed in all rats (male and female) during hours 1 to 4 of the exposure period. A few male rats exhibited reduction in bodyweight gain on the day following exposure. Subsequently though, bodyweight gain was similar to that observed in control rats. Food consumption was found to be slightly reduced in male rats for a single day while water consumption seemed unaffected following exposure to cyclopentane. One male rat also exhibited wet fur around the snout and jaws immediately following the exposure period.

 

No macroscopic abnormalities were noted in rats exposed to cyclopentane and individual findings such as basophilic cortical tubules in kidneys, macophage aggregates, alveolar hemorrhage and pneumonitis in the lungs were considered spontaneous in origin and not treatment-related. Lung to body-weight ratios were found to be within normal limits for all male and female rats.

 

Based on the results discussed above, the 4-hour inhalation LC₅₀ for cyclopentane is >25.30 mg/L. Cyclopentane is practically non-toxic in the acute inhalation toxicity test in rats. This study received a Kilmisch score of 1 and is classified as reliable without restrictions because it is in compliance with international guidelines for acute.

 

2-methylbutane

 

In a supporting study (Stoughton and Lamson, 1936), the effects of the anesthetic activity of isopentane on mice were tested. In the first test series, referred to as the "light anesthesia" test, two mice at a time were placed in a 2 liter bottle containing the isopentane gas mixture. During this test, mice were dosed at concentrations of 4.2, 4.9, and 5.4 mmol/L. If animals were unable to maintain their upright posture after spinning the bottle then they were said to be lightly anesthetized. For the three concentration levels tested, the time it took for mice to become lightly anaesthetized ranged from 2.2 to 11.6 minutes. No mice died during the first test series. In the second test series, referred to as the "complete anesthesia" test, five mice at a time were placed in a 20 liter bottle containing the isopentane gas mixture. During this test, mice were dosed at concentrations of 5.8 and 6.3 mmol/L. If animals were unable to regain their upright positioning after shaking then they were said to be anaesthetized. After two hours, the mice were removed from the bottle and the number of mortalities was noted. No mortalities occurred at 4.2, 4.9, or 5.4 mmol/L, 2 mortalities occurred at 5.8 mmol/L, and 5 mortalities occurred at 6.3 mmol/L. The average recovery time for the survivor test mice ranged from 4 to 8 minutes. While an LC₅₀ was not provided, the study results suggest that the LC₅₀ may be between 5.4 mmol/L and 5.8 mmol/L.

2 -Methylbutane, like other pentanes, is classified as Xn; R65, harmful: may cause lung damage if swallowed in accordance with Dangerous Substances Directive 67/548/EEC and as Category 1 for aspiration toxicity (H304: May be fatal if swallowed and enters airway) in accordance with CLP EU Regulation 1272/2008.

Justification for classification or non-classification

Based on available substance specific and read across data, 2 -methylbutane is minimally toxic via ingestion where the LD₅₀is >2000 mg/Kg, and by inhalation where the LC₅₀ is >25300 mg/m³. These findings do not warrant classification under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Although there were no acute studies identified for dermal exposure, physiochemical data suggests that absorption via the dermal route is not significant and that dermal toxicity is not a significant cause for concern. Additionally, it is generally assumed that exposure via the oral route leads to greater absorption of the substance compared with exposures via the dermal route. Oral exposure studies within pentanes did not report any potential for serious or severe toxicity by this route of exposure, therefore it is unlikely that toxicity via dermal exposure poses a significant risk.

2 -methylbutane is classified under EU CLP guidelines as a Category 1 aspiration hazard based on its physical and chemical properties (hydrocarbon fluid, viscosity ≤ 20.5 mm²/s).