5-methylheptan-3-one oxime

Endpoint summary

Description of key information

oral and dermal studies shown to be above limits for classification

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

there are no details on the method followed

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Sample Marking: 76-362, Stemone

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

2.05 g/Kg
3.2 g/Kg
5.0 g/Kg
6.25 g/Kg

No. of animals per sex per dose:

10

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 800 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 870 - <= 5 010

Dose (g/Kg)	Deaths / No. of Anmials	Observation Day
		1	2	3	4	5	6	7	8	9	10	11	12	13	14
2.05	1/10	0	1	0	0	0	0	0	0	0	0	0	0	0	0
3.2	5/10	3	1	0	0	1	0	0	0	0	0	0	0	0	0
5.0	8/10	7	1	0	0	0	0	0	0	0	0	0	0	0	0
6.25	7/10	2	5	0	0	0	0	0	0	0	0	0	0	0	0

Symptomatology

2.05 g/kg - lethargy, piloerection, flaccid;

3.2 g/kg -ataxia, lethargy, ptosis;

5.0 g/kg ataxia, loss of righting reflex;

6.25 g/kg - ataxia, lethargy, ptosis, piloerection

Necropsy	2.05 g/kg	3.2 g/kg	5.0 g/kg	6.25 g/kg
Liver blotchy	1	5	2	6
Lungs dark	0	4	8	7
Small intestine very red	0	3	5	2
blood around nose, mouth and eye	0	3	0	3
bloody urine	1	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 2000 mg/kg, therefore not classified for CLP

Executive summary:

An acute oral study was carried out on rats in high doses (>2000mg/Kg). The LD50 was determined to be 3.2 g/Kg, this is well above the category 4 classification limit of 2000 mg/Kg for CLP.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

oral gavage of varying quantities of material

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CFE ( now Crl-OFA(SD) )

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Carworth
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: 18 hours
- Housing: raised wire mesh cages
- Diet: Fox Blox - ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: substance applied neat, no vehicle used.

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg

Doses:

1.0, 2.5, 3.0, 3.5, 4.0, 5.0 ml/Kg

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no
- Other examinations performed: no data

Sex:

female

Dose descriptor:

LD50

Effect level:

3.5 mL/kg bw

Based on:

test mat.

95% CL:

>= 2.78 - <= 4.41

Mortality:

See table below, observations at the 2.5 ml/Kg concentration and above. No deaths were observed at the lowest concentraton of 1 ml/kg

Clinical signs:

other: no data

Gross pathology:

no data

Other findings:

no data

Results:

Dose (ml/kg)	Response	% Observed	% Expected	Observed Minimus Expected	(CHI)²
1.0	0/10	0 /10	0.46	0.46
2.5	3/10	30	28	2	0.0019
3.0	4/10	40	40	0	--
3.5	5/10	50	50	0	--
4.0	6/10	60	60	0	--
5.0	9/10	90	75	15	0.1180
					1.19

ED₈₄= 6.0

ED₅₀= 3.5

ED₁₆= 1.98

N¹ = 40

S = [(ED₈₄/ ED₅₀) + (ED₅₀/ ED₁₆)] / 2 = 1.741

fED₅₀= S²·⁷⁷/√N¹= 1.26

ED₅₀ x fED₅₀= 4.41

ED₅₀ / fED₅₀= 2.78

The oral LD50 was calculated to be 3.5 ml/Kg bw for female rats with a 19/20 confidence limit of 2.78 - 4.41 ml/Kg bw

Interpretation of results:

GHS criteria not met

Conclusions:

Given the density of the material, the LD50 of 3.5ml/Kg bw will be above the lowest classification criteria for CLP, therefore according to this data, the substance should not be considered acutely toxic via the oral route.

Executive summary:

Sixty normal, healthy, female Carworth rats were fasted for eighteen hours prior to dosing. The test material was administered orally, by rigid stomach tube, at several dose levels to groups of ten rats. No deaths were observed at the lowest dose level of 1.0 ml/Kg bw, the oral LD₅₀ was calculated to be 3.5 ml/Kg bw for female rats. Given the density of the material, the oral LD₅₀ of 3.5ml/Kg bw will be above the lowest classification criteria for CLP, therefore according to this data, the substance should not be considered actutely toxic via the oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 200 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:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

no details on the method are available.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Sample Marking: 76-362, Stemone

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Duration of exposure:

14 d

Doses:

2.5 g/kg
5.0 g/kg

No. of animals per sex per dose:

4 @ 2.5 g/kg
8 @ 5 g/kg

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Dose (g/Kg)	Deaths / No. of Anmials	Observation Day
		1	2	3	4	5	6	7	8	9	10	11	12	13	14
2.5	0/4	0	0	0	0	0	0	0	0	0	0	0	0	0	0
5.0	2/8	0	0	0	0	0	1	0	0	0	1	0	0	0	0

Slight redness in 1 at 5.0 g/kg

Moderate redness in others

Slight edema in 2 at 2.5 g/kg and 2 at 5.0 g/kg

Moderate edema in others

Necropsy - portion of small intestine reddened and evidence of diarrhea prior to death in 1.

Interpretation of results:

GHS criteria not met

Conclusions:

Dermal LD50 shown to be above 5000 mg/kg.

Executive summary:

An acute dermal toxicity study was carried out on Rabbits, the LD 50 was determined to be greater than the highest test dose of 5000 mg/kg, therefore the substance can be considered as not classified according to CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Justification for classification or non-classification

Two oral studies have shown the LD50 oral for Stemone to be greater than 2000mg/Kg, a dermal study showed that the LD50 was above 5000mg/kg, therefore it should be considered not classified for CLP for acute toxicity endpoints.