Butanone

Endpoint summary

Description of key information

The following information is taken into account for any hazard / risk assessment:

Information on the acute oral toxicity of methyl ethyl ketone was obtained from data on the read across substance , secondary butanol. Secondary butanol is reported to have low acute oral toxicity following oral administration. Reported oral LD50 values of secondary butanol were 2054 mg/kg body weight for males and 2328 mg/kg body weight for females in a study performed similar to test guidelines and in compliance with good laboratory practice. The overall calculated oral LD50 in rats was 2193 mg/kg body weight. Clinical signs included gait and/or posture abnormalities in all rats at all dose levels. In the higher dose groups some rats were comatose or prostrate within a few hours of dosing, with some animals being unconscious for 24 hours or more. In a supporting study, the oral LD50 for the registered substance itself, methyl ethyl ketone, in female Harlan-Wistar rats is reported to be 3460 mg/kg body weight (Cox, 1976); although the study does not meet the criteria of current guidelines for acute oral toxicity, it supports the conslusion that the substance is not acutely toxic via the oral router.

The dermal LD50 for methyl ethyl ketone in male rabbits was reported by Smyth et al. (1962). As discussed below, the study is lacking details, but is deemed reliable. The dermal LD50 in male rabbits is reported to be greater than 10 mL/kg body weight.

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:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation, for read-across substance

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

-reliability scoring was based on 2001 guideline

Deviations:

yes

Remarks:

-insignificant deviation, guideline suggests using animals of all the same sex; no necropsy conducted

GLP compliance:

yes

Test type:

acute toxic class 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: Charles River U.K. Ltd.
- Age at study initiation: 9 to 11 weeks old
- Weight at study initiation: Weight on Day 1 = 189 to 219 g (males) and 125 to 149 g (females)
- Fasting period before study: Fasted overnight (18 h) prior to dosing.
- Housing: Two days before dosing, the rats to be used were housed in groups of 2 or 3 animals of the same sex per cage.
- Diet (e.g. ad libitum): Food (PRD, Labsure Animal Foods, Dorset), ad libitum
- Water (e.g. ad libitum): Filtered but untreated water from the public supply, ad libitum
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): air temperature was 19 to 25 °C
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: not reported

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Range finding studies were performed.

Doses:

950, 1200, 1500, 2000, and 2400 mg/kg

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed for clinical signs over 14 days. Body weight measurements were recorded on Days 1, 7, and 14.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Statistics:

Acute oral LD50 values were calculated using probit analysis (Finney, 1977).

Sex:

male

Dose descriptor:

LD50

Effect level:

2 054 other: mg/kg

Remarks on result:

other: 95% fiducial limits were 1283 - 4018 mg/kg

Sex:

female

Dose descriptor:

LD50

Effect level:

2 328 other: mg/kg

Remarks on result:

other: 95% fiducial limits were 1470 - 5428 mg/kg

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 193 other: mg/kg

Remarks on result:

other: 95% fiducial limits were 1608 - 4146 mg/kg

Mortality:

Over the 14-day observation period, 0, 1, 2, 1, and 8 animals died in the 950, 1200, 1500, 2000, and 2400 mg/kg dose groups, respectively. For more details, refer to Table 1 (attached).

Clinical signs:

other: All rats at all dose levels had gait and/or posture abnormalities. In the higher dose groups some rats were comatose or prostrate within a few hours of dosing, with some animals being unconscious for 24 hours or more. Some rats in the top dose group (2400

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 193 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

1962

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study without detailed documentation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Missing information on test material, test animals, housing conditions, diet, environmental conditions, dermal exposure, vehicle, doses, examinations and measurements. No individual results were reported

GLP compliance:

no

Remarks:

Study pre-dates GLP requirements

Test type:

other: Similar to the cuff method of Draize et al.

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

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: 2.5 to 3.5 kg
- 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:

occlusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: entire trunk
- % coverage: Not reported
- Type of wrap if used: Plastic film


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not reported
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Not reported
- Concentration (if solution): Not reported
- Constant volume or concentration used: yes
- For solids, paste formed: Not reported


VEHICLE
No information

Duration of exposure:

24 hours

Doses:

Not specifically reported. It is reported that, dosages greater than 20 ml/kg can not be retained in contact with the skin.

No. of animals per sex per dose:

4 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- 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:

LD50 was reported to be calculated

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 mL/kg bw

Mortality:

Not reported

Clinical signs:

other: Not reported

Gross pathology:

Not reported

Other findings:

Not reported

No tables or results presented

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:

8 000 mg/kg bw

Additional information

Acute Toxicity: Oral

Information on the acute oral toxicity of methyl ethyl ketone was obtained from data on the read across substance, secondary butanol. Metabolic data demonstrate that secondary butanol (sBA) is rapidly and extensively converted to methyl ethyl ketone via oxidation of the alcohol functional group by alcohol dehydrogenase in the liver. Thus, methyl ethyl ketone may be used as an appropriate surrogate for sBA and vice versa considering that exposure to either substance would essentially result in exposure to methyl ethyl ketone. The potential acute oral toxicity study of secondary butanol 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. Groups of 5 males and 5 females were administered undiluted test article via gavage at dose levels of 950, 1200, 1500, 2000, or 2400 mg/kg body weight. Rats were observed for clinical signs over a 14 day observation period and body weights were measured on days 1, 7, and 14. No animals died in the 950 mg/kg body weight group, one animal died in each of the 1200 and 2000 mg/kg body weight groups, two animals died in the 1500 mg/kg body weight group, and eight animals died in the 2400 mg/kg body weight group. All rats at all dose levels had gait and/or posture abnormalities. In the higher dose groups, some rats were comatose or prostrate within a few hours of dosing, with some animals being unconscious for 24 hours or more. All animals had either died or recovered by day 3. All surviving rats had gained weight relative to their body weights by the end of the 14-day observation period. The LD50 for males was calculated to be 2054 mg/kg body weight with 95% confidence intervals of 1283 to 4018 mg/kg body weight. For females, the LD50 was calculated to be 2328 mg/kg body weight with 95% confidence intervals of 1470 to 5428 mg/kg body weight. Finally, the oral LD50 of secondary butanol for males and females was calculated to be 2193 mg/kg body weight with 95% confidence intervals of 1608 to 4146 mg/kg body weight.  

In addition, a supporting study for methyl ethyl ketone is included as a supporting reference. The potential acute oral toxicity of methyl ethyl ketone was assessed in female Harlan-Wistar rats (Cox, 1976). A number of methodology details were not reported; however, rats were administered the test-article by gavage and observed for 14-days for signs of toxicity. The LD50 in female rats was reported to be 4.29 mL/kg body weight. Based on a density of 805.4 g/L, the LD50 was calculated to be 3460 mg/kg body weight. Methyl ethyl ketone was not classified as acutely toxic according to CLP criteria (Registration (EC) No 1272/2008).

Please refer to the document attached to Section 13 for justification of read across.

Acute Toxicity: Dermal

The potential acute dermal toxicity of methyl ethyl ketone was assessed in male New Zealand White rabbits by Smyth et al. (1962). 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 et al.(1962) administered the test article to the entire trunk of the 4 male animals for 24 hours with an occlusive plastic film. The dermal LD50 of methyl ethyl ketone in male rabbits was determined to be greater than 10 mL/kg body weight.

Methyl ethyl ketone was not classified as acutely toxic following oral exposure according to CLP.

Acute Toxicity: Inhalation

In accordance with column 2 of REACH Annex VIII, the acute toxicity by inhalation study (required in section 8.5.2) does not need to be conducted as acute toxicity studies are available for the oral and dermal routes of exposure.

Justification for classification or non-classification

Acute Toxicity: 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 or dizziness), as set out in Regulation (EC) No. 1272/2008.