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Administrative data

Description of key information

Ethanol:
ORAL RAT LD50 values
Normal adults: female: 15: female: 15010mg/kg; male/female: 22500mg/kg
Young adults: Male: 10600mg/kg
veryYoung (<14 days): Male/female: 7800mg/kg
Old animals: male: 7060, Male/female: 14600mg/kg
Isopropanol:
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.
Ethanol:
INHALATION MOUSE
LC50(1hr) >60000ppm, EC50(1hr)=30300ppm
Isopropanol:
Rat LC50(6h)>10000 ppm (>25000 mg/m3)
Dermal
Isopropanol:
rabbit LD50 = 16.4 ml/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
25 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
13 900 mg/kg bw

Additional information

There are no data available for the reaction mass. Oral acute toxicity of the constituents is low. It is concluded that the oral LD50 value for the reaction mass is >2000 mg/kg bw (lowest reported for isopropanol is 5840 mg/kg bw). For the dermal and inhalatory route data are taken from isopropanol, which are considered to represent worst case values for the reaction mass.

Ethanol

ORAL ROUTE

In an acute toxicity study in female rats using a relatively large number of animals over 7 closely spaced doses, an LD50 value of 14500 -15500mg/kg was obtained. Animals were only observed for a period of 24 hours, although it is unlikely that significant deaths would have occurred after this point due to the known toxicokinetics of metabolism. Those animals that died showed severe CNS effects with death due to cardiorespiratory failure that was preceded by coma. An acute toxicity study examined the effect of age of male rats on the oral LD50. Using a relatively large number of animals and 6 -8 doses, an LD50 value of 10600mg/kg was obtained for young animals (~100 days old) whereas a significantly lower figure of 7060mg/kg was obtained for older rats (~11 -12 months old). Animals were only observed for a period of 24 hours, although it is unlikely that significant deaths would have occurred after this point due to the known toxicokinetics of metabolism. For those animals that died death was due to respiratory failure. An acute toxicity study, for which only basic experimental detail is reported, examined the effect of age of rats on the oral LD50, which was obtained for three groups of animals: immature 14 day old animals, young and old adults. The study clearly demonstrated that both old and young animals are more sensitive to toxic effects than are young adults, which supports the results from other studies. The study also looked at the effects of ethanol on newborn animals. Whilst it was not possible to quantify the LD50, the study confirmed the hypothesis that they are more sensitive.  Overall, ethanol is of low toxicity by the oral route. The LD50 for adult animals is in the range 14500mg/kg upwards. The data suggest an assessment factor of 2 is appropriate if predictions of toxicity to the old and young is required.

DERMAL ROUTE

No reliable data available. The LD50 oral can be used as a starting point and an appropriate factor for dermal uptake used to estimate dermal acute toxicity.

INHALATION ROUTE

In an acute toxicity inhalation study, mice were exposed to ethanol for different periods of time up to 1 hour in order to determine the LC50 and the EC50 for motor performance. An LC50 could not be obtained for inhalation exposure; no deaths were reported for exposures up to 60,000ppm (114mg/l), which can be considered the saturated vapour concentration. In the motor performance test, an EC50 60 min value of 30,300ppm was established, with a slope for the dose effect curve of 12.6. This result differered only slightly from the EC50 30 min. Whilst exposures were only for 1 hour, the evidence suggests that exposures for 4 hours would not have significantly reduced the motor performance results or the LC50. It should be noted that all of the reported EC50 values are above the lower explosive limit reported in chapter 4. Based on this information, inhalation exposure poses little acute hazard at any feasible exposure concentration.

Isopropanol

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 documentsviasecondary references. Therefore, the results reported by this group are deemed reliable. In their investigation, Smyth

and Carpenter (1948) determined the LD50 ofisopropanol in rats to be 5840 mg/kg body weight as assessed following oral gavage administration of a range of isopropanolconcentrations 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 dermal 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 Guidelines for the Testing of Chemicals No. 403 and in compliance with Good Laboratory Practice (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 LC50 was> 10,000ppm

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

Justification for classification or non-classification

Based on data for the two constituents it can be concluded that the reaction mass does not need to be classified for acute toxicity according to DSD or CLP.

However, as isopropanol is classified for specific target organ toxicity the reaction mass will also be classified as H336 according to CLP.

Ethanol:

All LD50 and LC50 are by some margin above the thresholds for classification for acute toxicity either under directive 67/548 or the EU CLP regulations.

Isopropanol

The substance does not meet the criteria for classification and labelling for this endpoint, as set out in 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 Regulation (EC) No. 1272/2008.