Acetone oxime

Endpoint summary

Description of key information

The substance is of low acute toxicity to mammals by the oral route but is harmful by the dermal route.

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

Reliability:

2 (reliable with restrictions)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Substance dosed at 10ml/kg

Doses:

0, 300, 1000 and 3000 mg/kg.

No. of animals per sex per dose:

5 per sex per dose. The study also includes additional satellite groups of 5 per sex per dose for haematology evaluations only.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1,2 and 4 hours after dosing and then daily
- Frequency of weighing: Body weights were obtained prior to dosing and on days 1, 4, 7, 11 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: neurological examinations, haematology, organ weights, histopathology

Statistics:

Body weights, haematology data, organ weights and organ/body weight rations were analysed statistically.

Preliminary study:

In a preliminary sighting study 2/2 animals died at 5000 mg/kg.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Based on:

act. ingr.

Mortality:

1/5 males died at 3000 mg/kg

Clinical signs:

Unusual signs were seen primarily in the high-dose group and consisted of ataxia in a few animals and hypoactivity and decreased food consumption in several animals. Ataxia was seen only on the day of dosing, while hypoactivity was evident for up to four days after dosing. Decreased food consumption was apparent from Days 2 through 4. All survivors in this group were free of significant abnormalities from Day 5 through study termination. Neurologic examinations on the day of dosing revealed no abnormal reflexes or other indications of neurologic impairment; neurologic examinations on Days 7 and 14 revealed no abnormalities in this group. Abnormalities in the mid-dose group were limited to single observations (in one animal) of ataxia and hypoactivity two hours post-dose and dedreased food consumption in a second animal on Days 2 and 3. No significant abnormalities were seen in the control or low-dose groups.

Body weight:

Dose-related, reversible, decreases in body weights with subsequent gains were apparent in all treated groups. Complete recovery (weights and
weight gains comparable to control values) was evident in low-dose animals by Day 7, while weights and weight gains for mid- and high-dose animals remained slightly or moderately lower than control values for the remainder of the study.

Gross pathology:

Gross postmortem examination revealed no apparent effects of test material administration. However, spleen weights for all treated groups of animals were higher than control weights, although no dose-relationship was evident. Microscopic examinations revealed alterations in the spleen which occurred with greater frequency and/or severity in treated than in control animals, generally without any clear dose relationship. Changes consisted of increased severity of extramedullary hematopoiesis and increased severity and/or incidence of the presence of pigment in reticuloendothelial cells.

Other findings:

Acetone Oxime produced dose-related methemoglobinemia on Day 1 and a reversible anemia which was evident on Days 4 and/or 14 but not at Day 28. Effects included decreased hemoglobin, hematocrit and total erythrocyte values, elevated reticulocyte counts and elevated mean corpuscular volume, hemoglobin and hemoglobin concentrations. Mean total leukocyte counts were elevated in high-dose males and females at Day 4 but not on Days 14 or 28. Evaluations of differential leukocyte counts performed on Day 4 revealed a greater elevation in segmented neutrophils than in lymphocytes. Small numbers of nucleated erythrocytes were seen in blood smears obtained from treated animals at Days 4 and/or 14. Differential counts and erythrocyte morphology at Day 28 were considered unremarkable.

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 for acetone oxime is > 3000 mg/kg

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 000 mg/kg bw

Quality of whole database:

Sufficient to meet data requirements. The study is Klimisch 2.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

An acute inhalation toxicity study is scientifically unjustified and is not in the interests of animal welfare. Acute studies are available by the oral and dermal routes.

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

Reliability:

2 (reliable with restrictions)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

water

Duration of exposure:

24 hours

Doses:

0, 100, 500 and 1000 mg/kg

No. of animals per sex per dose:

5 per sex per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: 1,2 and 4 hours after dosing and then daily
- Frequency of weighing: Body weights were obtained prior to dosing and on days 1, 4, 7, 11 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: neurological examinations, haematology, organ weights, histopathology

Statistics:

Body weights, haematology data, organ weights and organ/body weight rations were analysed statistically.

Preliminary study:

In a preliminary study 1/2 animals died at 1000 mg/kg and 2/2 animals died at 2000 mg/kg

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No animals died in the main study

Clinical signs:

At 1000 mg/kg hypoactivity, fecal staining and a darkened iris were seen following dosing and poor food consumption on Day 3. At the lower doses only fecal staining was observed. All animals free of clinical signs from Day 4 of the study. Neurological examination revealed no unusual signs in any animal.

Body weight:

Body weights of test animals were comparable to controls.

Gross pathology:

No effects noted on organ weights or gross pathology. Microscopic pathology revealed myeloid and erythroid hypercellularity of the femoral bone marrow in all top dose animals and 4/10 mid dose animals.

Other findings:

Dose related methaemogloburia was noted on days 1 and/or 5 but not at study termination. Marked differences were noted in most haematology parameters in the top dose animals.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 for acetone oxime is > 1000 mg/kg

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

Sufficient to meet data requirements. The study is Klimisch 2.

Additional information

The substance is of low to moderate acute toxicity in mammals. In a reliable acute oral study in rats, 1/10 animals died at the top dose of 3000 mg/kg. In the preliminary oral sighting study 2/2 animals died at 5000 mg/kg. Hence the oral LD50 is >3000 mg/kg. In a reliable acute dermal study in rabbits, toxicity but no mortalities were observed at the top dose of 1000 mg/kg. In the preliminary dermal sighting study 1/2 animals died at 1000 mg/kg and 2/2 animals died at 2000 mg/kg. Hence the dermal LD50 is >1000 mg/kg. There are also several published literature studies on the substance which used other dose routes. However these are all unreliable.

 

The results are consistent with those found for the read-across candidate butanone oxime (CAS 96-29-7), which gave an acute oral LD50 of 2326 mg/kg and an acute dermal LD50 of >1000 mg/kg.

Justification for selection of acute toxicity – oral endpoint
Only one study available on the substance.

Justification for selection of acute toxicity – dermal endpoint
Two studies available on the substance however this study is the more reliable.

Justification for classification or non-classification

On the basis of the acute toxicity results the substance does not meet the criteria for classification by the oral route. However it does meet the criteria for classification by the dermal route Acute tox. 4, H312.