Acetone oxime

Carcinogenicity

Description of key information

The substance was reported to give a carcinogenic response in male rats.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Numerous deficiencies in the conduct of the study. For example the study had only one dose group and the group size was too small. The control group was non-concurrent. The study was not conducted to any guideline and there is no data regarding GLP. The study is only very briefly reported.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Substance tested by administration in the drinking water to male and female outbred MRC-Wistar rats. The dose of 1.0 g/L was administered 5 days/week for 18 months.

GLP compliance:

not specified

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: drinking water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

18 months

Frequency of treatment:

5 days per week

Remarks:

Doses / Concentrations:
1000mg/l
Basis:
nominal in water
Total dose = 7g/rat (males) and 6.2 g/rat (females)

No. of animals per sex per dose:

15 males and 16 females

Control animals:

other: The control animals were given no treatment. The controls and treated animals were started 8 months apart since the former also served as controls for other studies

Observations and examinations performed and frequency:

BODY WEIGHT: Yes
- Time schedule for examinations: Monthly

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: For selected cages, over 24 hr periods every month

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

Not reported

Body weight and weight changes:

effects observed, treatment-related

Water consumption and compound intake (if drinking water study):

not specified

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

Liver tumors were present, chiefly in the male rats [80% incidence (93 wk)] but also in the females [17% incidence (111 wk)J. For males only, the liver tumor incidence was significantly greater than the 0% incidence in the controls. All rats with liver tumor had hepatocellular adenomas, mostly 1-4 cm in diameter. These were composed of circumscribed masses of cells, having abundant cytoplasm and small, round nuclei. All these tumors had benign histologic criteria despite occasional differences in nuclear size, except in 1 male rat in which focal malignant degeneration was noted. Three rats (including 2 males) had liver hemangiomas in addition to the adenomas.

Dose descriptor:

LOAEL

Effect level:

<= 1 000 mg/L drinking water

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Incidence of liver tumours

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Dose descriptor:

LOAEL

Effect level:

> 1 000 mg/L drinking water

Based on:

test mat.

Sex:

female

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Conclusions:

Acetone oxime was a liver carcinogen to male rats in this study. However there were numerous deficiencies in the conduct of this study. For example the study had only one dose group and the group size was too small. The control group was non-concurrent. The study was not conducted to any guideline and there is no data regarding GLP. The study is also only very briefly reported. Hence the study has been assessed as unreliable.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Study duration:

chronic

Species:

rat

Quality of whole database:

This study is in excess of requirements however is included as available data.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Whilst the available carcinogenicity study gave a positive result, the study design and reporting means that it is assessed as unreliable. Hence of itself this study would not justify classification. However the structurally related substance butanone oxime (CAS No. 96-29-7) has been tested in chronic studies in both rats and mice and also gave rise to liver carcinogenicity in male animals only, in both species. Butanone oxime is classified as a Carcinogen, category 2. Given the close structural similarity between the two substances and the similarity of findings between the available chronic data, the registrant proposes a precautionary approach to classify acetone oxime as a Carcinogen, category 2, H351.

Additional information

The substance was dosed to rats in drinking water for 18 months.Liver tumors were present, chiefly in the male rats [80% incidence (93 wk)] but also in the females [17% incidence (111 wk)J. For males only, the liver tumor incidence was significantly greater than the 0% incidence in the controls. All rats with liver tumor had hepatocellular adenomas, mostly 1-4 cm in diameter. These were composed of circumscribed masses of cells, having abundant cytoplasm and small, round nuclei. All these tumors had benign histologic criteria despite occasional differences in nuclear size, except in 1 male rat in which focal malignant degeneration was noted. Three rats (including 2 males) had liver hemangiomas in addition to the adenomas. However there were numerous deficiencies in the conduct of this study. For example the study had only one dose group and the group size was too small. The control group was non-concurrent. The study was not conducted to any guideline and there is no data regarding GLP. The study is also only very briefly reported. Hence the study is assessed as unreliable and the validity of the results is uncertain.

Justification for selection of carcinogenicity via oral route endpoint:
It is the only available carcinogenicity study however it is an unreliable study.

Carcinogenicity: via oral route (target organ): digestive: liver