Propan-2-ol

Endpoint summary

Description of key information

Isopropanol is associated with low acute oral toxicity. The oral LD50 was reported to be 5840 mg/kg body weight in rats administered the test article by gavage (Smyth and Carpenter, 1948). No other study details were provided.

Isopropanol is associated with low acute dermal toxicity following dermal exposure. Smyth and Carpenter (1948)  reported a dermal LD50 for isopropanol of 16.4 mL/kg body weight in rabbits.

Isopropanol was reported to be well tolerated in rats at inhalation exposures up to 1500 ppm for 6 hours (Gill, 1991). At higher dose levels (5000 and 10000 ppm) a number of clinical signs were observed, including transient central system sedation and reversible narcosis. No mortalities were observed at exposures up to 10000 ppm.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1948

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

reliability scoring based on 2001 guideline for Test No. 423

Deviations:

yes

Remarks:

Lacking detail in methodology and results

GLP compliance:

no

Remarks:

Study pre-dates GLP requirements

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sherman

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- Fasting period before study: Not reported
- Housing:Not reported
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum):Not reported
- Acclimation period:Not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light):Not reported


IN-LIFE DATES: Not reported

Route of administration:

oral: unspecified

Vehicle:

acetone

Details on oral exposure:

No information provided

Doses:

Not reported. The authors state rats are given dosages differeing in a ratio of 10.

No. of animals per sex per dose:

6 rats/dose group

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days (or other?); Not reported
- Frequency of observations and weighing: Not reported
- Necropsy of survivors performed: Not reported
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Not reported

Statistics:

Not reported

Preliminary study:

NA

Sex:

not specified

Dose descriptor:

LD50

Effect level:

5.84 other: g/kg body weight

Mortality:

Not reported

Clinical signs:

other: Not reported

Gross pathology:

Not reported

Other findings:

Not reported

Interpretation of results:

GHS criteria not met

Executive summary:

The work of this group pre-dates range finding toxicity guidelines and provided much of the basis for their development. Their results are cited by many subsequent authoritative review bodies and are often found in SIDS and SIAR documents via secondary references. Therefore, these results are deemed reliable.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 840 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guidelines

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

6 hr exposure period instead of 4 hr, 14-day observation period was not clearly stated

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Spague-Dawley, Inc. (Indianapolis, IN)
- Age at study initiation: 9 to 11 weeks
- Housing: individually in stainless stell wire mesh cages
- Diet (e.g. ad libitum): Ground Purina Certified Rodent Chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 25
- Humidity (%): 40 to 70
- Photoperiod (hrs dark / hrs light): 12/12

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: stainless steel chambers with glass doors and windows
- Exposure chamber volume: Four approximately 1330-liter and one approximately 900-liter
- Source and rate of air: filtered air at a flow rate of approximately 14 air changes per hour
- Temperature, humidity in air chamber: recorded approximately 12 times during each exposure

TEST ATMOSPHERE
- Brief description of analytical method used: flame ionization gas chromatographic (GC) technique
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 6 h

Concentrations:

500, 1500, 5000, 10000 ppm

No. of animals per sex per dose:

25 animals/sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: twice daily, beginning on the day of after exposure and continuing until sacrifice
- Frequency of observations and weighing: body weights were recored prior to exposure and during each test session
- Necropsy of survivors performed: no

Statistics:

The data for continuous, parametric variables were intercompared for the dose and control groups by use of Levene’s test for homogeneity of variances,by analysis of variance, and by pooled variance t-tests. The t-tests were used, if the analysis of variance was significant (P
Intra-session motor activity data was analyzed using a repeated measures analysis with dose as grouping factor and session time as the within subject factor. Group comparisons at each reporting epoch were made (as described above) if significant dose effects or time by dose interactions were observed.
The epsilon-adjustment procedure (Greenhouse-Geisser correction) was used in repeated measures analysis of motor activity data.
Frequency data from FOB tests was evaluated using Fisher’s exact
probability test.

All statistical tests were performed using BMDPm Statistical Software (Dixon, 1985 or Dixon, 1988). The fiducial limit of 0.05 was used as the critical level of significance for all tests.

Sex:

male/female

Dose descriptor:

other: transient, concentration-related narcosis and/or central nervous system sedation

Effect level:

ca. 5 000 ppm

Exp. duration:

6 h

Sex:

male/female

Dose descriptor:

other: transient, concentration-related narcosis and/or central nervous system sedation

Effect level:

ca. 10 000 ppm

Exp. duration:

6 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 10 000 ppm

Exp. duration:

6 h

Mortality:

none

Clinical signs:

other: In the 10000 ppm group, prostration, severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular tone, hypothermia, and loss of reflex function was observed 1 and 6 hours after exposure. Concentration-related decreases in mean

Body weight:

Body weight was measured at the time of behavioral testing so that any possible confounding effect that body weight might have on behavior could be assessed. Mean body weights for the five exposure groups were not statistically significantly different at any time during the study. Mean body weight tended to be lower for animals in the 10000 ppm exposure group assigned to FOB testing at the 6-hour and 24-hour post-exposure evaluations. This decrease is considered to reflect decreased food consumption during the time period when prostration and narcosis were observed.

Gross pathology:

none

Interpretation of results:

GHS criteria not met

Remarks:

for acute toxicity

Conclusions:

LC50 > 10000 ppm

Executive summary:

Due to transient concentration-related narcosis and central nervous system sedation effects, the substance should be classified under STOT single exposure category 3, H336 - may cause drowsiness or dizziness, according to CLP classification criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

25 000 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1948

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Lack of methodological details

GLP compliance:

no

Remarks:

study pre-dates GLP requirements

Test type:

other: Not reported

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- Fasting period before study: Not reported
- Housing:Not reported
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum):Not reported
- Acclimation period:Not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light):Not reported


IN-LIFE DATES: Not reported

Type of coverage:

other: rubber cuff

Vehicle:

other: carbitol

Details on dermal exposure:

TEST SITE
- Area of exposure: Not reported
- % coverage: Not reported
- Type of wrap if used: rubber cuff


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not reported
- Time after start of exposure:Not reported


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Not reported, the authors stated that dosages as great as 20 ml/kg can be retained by the cuff.



VEHICLE
- Amount(s) applied (volume or weight with unit): Not reported

Duration of exposure:

24 hours

Doses:

Not reported, the authors stated that dosages as great as 20 ml/kg can be retained by the cuff.

No. of animals per sex per dose:

It is reported that the number of animals used are similar to those given oral dosages. The oral LD50 section reports groups of 6 rats.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days (or other?); Not reported
- Frequency of observations and weighing: Not reported
- Necropsy of survivors performed: Not reported
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Not reported

Statistics:

Not reported

Preliminary study:

NA

Sex:

not specified

Dose descriptor:

LD50

Effect level:

16.4 mL/kg bw

Mortality:

Not reported

Clinical signs:

other: Not reported

Gross pathology:

Not reported

Other findings:

Not reported

Interpretation of results:

GHS criteria not met

Executive summary:

The work of this group pre-dates range finding toxicity guidelines and provided much of the basis for their development. Their results are cited by many subsequent authoritative review bodies and are often found in SIDS and SIAR documents via secondary references. Therefore, these results are deemed reliable.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

13 900 mg/kg bw

Additional information

Acute Toxicity: Oral

The potential acute oral toxicity of isopropanol was assessed in rats by Smyth and Carpenter (1948). Although this study is lacking in methodological details, the work of this group pre-dates range finding toxicity guidelines and provided much of the basis for their development. Their results are cited by many subsequent authoritative review bodies and are often found in SIDS and SIAR documents via secondary references. Therefore, the results reported by this group are deemed reliable. In their investigation, Smyth and Carpenter (1948) determined the LD50 of isopropanol in rats to be 5840 mg/kg body weight as assessed following oral gavage administration of a range of isopropanol concentrations in acetone (vehicle) to groups of 6 Sherman rats (reported as 10, 1, 0.1, etc. g/kg body weight). Ispropanol was not classified as acutely toxic following oral exposure according to CLP.

 

Acute Toxicity: Dermal

As described above, the work of Smyth and Carpenter (1948) lacks methodological details but is deemed reliable. These authors examined the potential acute dermal toxicity of isopropanol in 6 rabbits after 24 hours of exposure and reported the LD50 as 16.4 mL/kg body weight. Isopropanol was not classified as acutely toxic following oral exposure according to CLP.

 

Acute Toxicity: Inhalation

The potential acute inhalation toxicity of isopropanol was assessed in Fischer 344 rats in a study similar in methodology to OECD Test Guideline 403 and in compliance with GLP (Gill, 1991). Groups of 25 male and 25 female rats were exposed (whole-body) to vapor concentrations of 0, 500, 1500, 5000, or 10000 ppm for 6 hours. The animals were placed in steel chambers with glass doors and windows. The animals were observed for signs of toxicity twice daily and body weights were recorded prior to exposure and at 6 and 24 hours post exposure. No animals died during the study. There were no significant effects on body weight with the exception of a decrease in the 10000 ppm group. The authors reported that this decrease reflected the decrease in food consumption observed during times of prostration and narcosis. In the 5000 ppm group, transient central system sedation was reported in males and females and in the 10000 ppm group reversible narcosis was observed. In the 10000 ppm group, prostration, severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular tone, hypothermia, and loss of reflex function was observed 1 and 6 hours after exposure. Concentration-related decreases in mean motor activity were observed for males in the 1500, 5000, and 10000 ppm groups and females in the 5000 and 10000 ppm groups. Motor activity was severely depressed for males and females in the 10000 ppm group. Exposure-related behavioral changes were not observed in the 500 ppm group. The LD50 was > 10 000 ppm

Isopropanol was not classified as acutely toxic following oral exposure according to CLP.

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for acute toxicity according to Regulation (EC) No. 1272/2008.

Specific target organ, Neurotoxicity: According to CLP classification criteria, the substance does meet the criteria for classification and labelling for this endpoint (STOT single exposure category 3, H336 - may cause drowsiness and dizziness) as set out in Annex VI of Regulation (EC) No. 1272/2008.