Cyclohexanone oxime

Endpoint summary

Description of key information

The oral LD50 of cyclohexanone oxime (CHO) was 883 mg/kg bw in female and 1765 mg/kg bw in male rats, respectively. 
No information is available for the inhalation route.
The dermal LD50 in rabbits was > 5000 mg/kg bw. 

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:

30. Jan 1979 to 28. Feb 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to guideline OECD 401 with acceptable restrictions, limited documentation

Qualifier:

according to guideline

Guideline:

other: EPA guideline (not further specified)

GLP compliance:

not specified

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: CHarles River Breeding Laboratory, Wilmington, USA
- Weight at study initiation: 145-236 g (males) and 138-163 g (females)
- Fasting period before study: overnight
- Housing: groups of two
- Diet (ad libitum): Purina laboratory chow
- Water (ad libitum): source not stated
- Acclimation period: 7 days

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg

Doses:

males: 562, 794, 1000, 1410, 1590, 2000 and 5000 mg/kg
females: 398, 631, 1000, 2000 and 5000 mg/kg

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:clinical observations immediately after dosing, then after 1 and 4 h, and twice daily thereafter
- Necropsy of survivors performed: yes

Statistics:

Probit analysis according to Finney

Sex:

male

Dose descriptor:

LD50

Effect level:

1 765.01 mg/kg bw

Based on:

test mat.

95% CL:

1 632 - 1 908.62

Remarks on result:

other: Acc. to study report: data obtained excluding the results of the 1000 mg/kg group; including this group the LD50 was 1758.94 (95% CI: 1374.74-2250.52) mg/kg

Sex:

female

Dose descriptor:

LD50

Effect level:

882.82 mg/kg bw

Based on:

test mat.

95% CL:

725.88 - 1 073.69

Mortality:

Mortality in males:
562 mg/kg: 0
794 mg/kg: 0
1000 mg/kg: 3
1410 mg/kg: 0
1590 mg/kg: 3
2000 mg/kg: 8
5000 mg/kg: 10

Mortality in females:
398 mg/kg: 0
631 mg/kg: 2
1000 mg/kg: 6
2000 mg/kg: 10
5000 mg/kg: 10

Clinical signs:

Surviving animals: transient slight to marked depression, rough hair coat, salivation, urine stains, ataxia in all dose groups for 1 - 4 h after administration (up to 2 days at higher doses)
labored respiration, prostration before death

Body weight:

not recorded

Gross pathology:

Discoloration of the spleen was noted in ten male rats dosed at 794 mg/kg of body weight, and in seven males dosed a t the 1590 mg/kg level. Discoloration of the stomach and/or intestines was observed in two males dosed a t the1000 mg/kg level, two males dosed at the 1590 mg/kg level, and four females dosed at 2000 mg/kg of body weight. Dark fluid was observed in the stomach and/or intestines of one male dosed a t 1000 mg/kg of body weight, three males dosed at the 1590 mg/kg level, one female dosed at the 631 mg/kg level, and three females dosed at the 1000 mg/kg level. Compound was noted in the stomach and/or intestines of two males dosed at the 1590 mg/kg level, in seven males and nine females dosed at the 2000 mg/kg level, and in all ten males and females dosed a t the 5000 mg/kg level.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the test substance the LD50 in rats was 883 mg/kg bw for females and 1765 mg/kg bw for males. Therefore the substance has to be classified as harmful if swallowed according to Regulation (EC) No 1272/2008

Executive summary:

The test substance was evaluated for acute oral toxicity in male and female Fischer 344 rats in a study performed according to EPA guidelines (similar to guideline OECD 401). Groups of 10 animals per sex were exposed to 562, 794, 1000, 1410, 1590, 2000 or 5000 mg/kg (males) or 398, 631, 1000, 2000 or 5000 mg/kg (females). After exposure the animals were observed for 14 days. Surviving animals showed transient slight to marked depression, rough hair coat, salivation, urine stains, and ataxia in all dose groups for 1 - 4 h after administration (up to 2 days at higher doses). Labored respiration and prostration was evident before death. Based upon the findings of this study, the acute oral LD50 was calculated to be 1765.01 and 882.82 mg/kg bw, with 95% confidence limits for males from 1632.20 to 1908.62 mg/kg bw and for females from 725.88 to 1073.69 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

882 mg/kg bw

Quality of whole database:

reliable LD50 in female rats

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:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Equivalent to guidellne with limited documentation

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

additional: haematology performed

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Davidson Mill Farms, NJ, USA
- Acclimation period: at least 14 days

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

Exposure to back skin shaved 24 h prior to application

Duration of exposure:

24 h

Doses:

0, 0.8, 2 or 5 g/kg bw

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations: daily; weighing: days -14, -7, 0 (day of exposure), 1, 4, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: spleen weights determined at end of study, blood was taken on days 1, 4 and 7 and haematology was performed

Statistics:

no data

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

not observed

Clinical signs:

not observed

Body weight:

not altered

Gross pathology:

no effects observed

Other findings:

- Organ weights: no effects on spleen weight
- Potential target organs: blood
- Other observations: haematology: dose-related increase in reticulocyte counts in both sexes, statistically significant only in males at highest dose, further effects: dose-related decrease in haemoglobin in females, significant at highest dose on day 7; dose-related increase in methaemoglobin in both sexes at day 4

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the dermal LD50 was > 5000 mg/kg bw. No classification is required.

Executive summary:

New Zealand white rabbits (5 per sex and dose) were tested for acute dermal toxicity in a study equilvalent to guideline OECD 402. They were exposed to 0, 800, 2000 or 5000 mg/kg bw of the test substance dermally for 24 h under an occlusive patch and observed for 14 days. No animal died at any dose level. There were no adverse clinical signs, body weight or organ weight changes associated with treatment. Haematological effects (all dose-related: increased reticulocyte counts, significant at highest dose only in in males; decreased haemoglobin values in females, significant at highest dose on day 7; increased methemoglobin levels in both sexes at day 4) indicate systemic uptake of the test substance.

Under the conditions of this study the dermal LD50 was > 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

reliable LD50 > 5000 mg/kg bw

Additional information

Oral exposure

Based on a reliable study (according to EPA guidelines, similar to guideline OECD 401, RL2) in male and female rats, the acute oral LD50 was calculated to be 1765.01 mg/kg bw (95% confidence interval 1632.20 to 1908.62 mg/kg bw) in males and 882.82 mg/kg bw (725.88 to 1073.69 mg/kg bw) in females. Support comes from a reliable study by Derelanko et al. (1985) with subacute exposure duration (10 exposures within 14 days), where no mortality was observed at doses up to 300 mg/kg bw/day, the highest dose tested.

Inhalation exposure

This information is not available. In accordance with column 2 of section 8.5 of REACH Annex VIII, an acute inhalation toxicity study is not necessary, because information is available for the oral and dermal route.

Dermal exposure

No mortality was observed after acute dermal exposure of rabbits in a reliable study (similar to OECD guideline 402, RL2) with doses up to 5000 mg/kg bw. Thus the dermal LD50 was > 5000 mg/kg bw.

 

Justification for selection of acute toxicity – oral endpoint
reliable study (Klimisch 2)

Justification for selection of acute toxicity – dermal endpoint
reliable study (Klimisch 2)

Justification for classification or non-classification

Oral LD50 values for male and female rats lie within the range of 300-2000 mg/kg bw. Therefore, CHO has to be classified for acute toxicity according to Regulation (EC) 1272/2008 as “harmful if swallowed” (H302).

No information is available for inhalation exposure.

No classification is required for dermal exposure because the LD50 was > 5000 mg/kg bw.