Methyl 3-pyridyl ketone

Endpoint summary

Description of key information

Acute Toxicity oral: acute oral gavage study, Sprague-Dawley rats, m/f, 0.0312 mL/kg , 0.0442 ml/kg and 0.0625 mL/kg in 10% (v/v) in 0.25% methyl cellulose: LD50 = 57 mg/kg (males), LD50 = 51 mg/kg (females), Toxicity Cat. III
Acute Toxicity oral: acute oral gavage study, wild-trapped birds: LD50 values are for Agelaius phoeniceus (redwinged blackbird): 178 mg/kg bw; Sturnus vulgaris (European starling): 1000 mg/kg bw; Coturnix coturnix (Coturnix): 422 mg/kg bw; Passer domesticus (House sparrow): >1000 mg/kg bw
Acute Toxicity oral: acute oral study, rat: LD50 = 46 µl/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

other: publication

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well-documented publication, which meets basic scientific principles

Principles of method if other than guideline:

The test article was administered by gavage as single doses to groups of young adult Harlan Sprague-Dawley rats (5/sex/group) at three dosage levels ranging from 0.0312 ml/kg to 0.0625 mL/kg.

GLP compliance:

not specified

Test type:

other: no information available

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Rats were fasted overnight (approximately 18 hours) before dosing

Route of administration:

oral: gavage

Vehicle:

other: 10% (v/v) in 0.25% methyl cellulose

Doses:

0.0312 mL/kg , 0.0442 ml/kg and 0.0625 mL/kg.

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

The test article was administered by gavage as single doses to groups of young adult Harlan Sprague-Dawley rats (5/sex/group) at three dosage levels ranging from 0.0312 mL/kg to 0.0625 mL/kg. The rats were fasted overnight (approximately 18 hours) before dosing. Dosed rats were observed frequently for signs of toxic effects on the first day of the study and twice a day thereafter except for weekends when the rats were examined for survival. Individual body weights were recorded on the day of dosing, and at 7 and 14 days after dosing. After 14 days, all survivors were sacrificed. Necropsies were performed on all animals that died or were sacrificed.

Sex:

male

Dose descriptor:

LD50

Effect level:

57 mg/kg bw

Based on:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

51 mg/kg bw

Based on:

not specified

Mortality:

see table 1

Clinical signs:

other: Clinical signs included sluggishness, an unsteady gait, gasping, pale extremities, prostration, convulsions, emaciation, a red crust on the perinasal and periocluar fur, and blood in the urine.

Gross pathology:

Necropsy of rats that died revealed red and/or mottled lungs, red or brown stomachs, discolored intestines (yellow to red) and dark red livers. Survivors had no remarkable lesions

Table 1 :

Dosage (mL/kg)	Number of rats dosed	Number of Deaths	Days to Death
0.0625	5 M	5	0,0,0,1,1
	5 F	5	0,1,1,1,1
0.0442	5 M	0	- -
	5 F	2	2,7
0.0312	5 M	0	- -
	5 F	0	- -

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 was reported as 57 mg/kg (males) and 51 mg/kg (females) in the rat.

Executive summary:

The test article was administered by gavage as single doses to groups of young adult Harlan Sprague-Dawley rats (5/sex/group) at three dosage levels ranging from 0.0312 mL/kg to 0.0625 mL/kg. The rats were fasted overnight (approximately 18 hours) before dosing. Dosed rats were observed frequently for signs of toxic effects on the first day of the study and twice a day thereafter except for weekends when the rats were examined for survival. Individual body weights were recorded on the day of dosing, and at 7 and 14 days after dosing. After 14 days, all survivors were sacrificed. Necropsies were performed on all animals that died or were sacrificed.

The acute oral LD50 was reported as 57 mg/kg (males) and 51 mg/kg (females) in the rat .

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

51 mg/kg bw

Quality of whole database:

There are three studies available on acute oral toxicity, one Klimisch 2 on rats, and two Klimisch 4 on either wild birds and rats. The Klimisch 2 studies reveals very similar LD50 values for male and female rats, and the Klimisch 4 supporting study on rats reveals consistently a similar value. Hence, the result can be considered as sufficiently reliable as they are consistent and plausible, the tonnage-driven data requirements under REACH are fully met, and the database is of good quality.

Additional information

There are three studies available on acute oral toxicity. The most reliable one, assessed with Klimisch 2, which is the best documented, and closest to standard procedures and test animals. The obtained results are LD50 = 57 mg/kg (males), and LD50 = 51 mg/kg (females). Hence, this study should be chosen due to its reliability as the one used for risk assessment, and therein the LD50 value of the more sensitive sex out of precautionary reasons.

The acute oral study on birds may serve as supporting study, as birds are a non-standard species for this endpoint and less relevant for humans than mammals. Besides, the rather high LD50 values (Agelaius phoeniceus (redwinged blackbird): 178 mg/kg bw; Sturnus vulgaris (European starling): 1000 mg/kg bw; Coturnix coturnix (Coturnix): 422 mg/kg bw; Passer domesticus (House sparrow): >1000 mg/kg bw) compared to rats indicate that the chosen key value for risk assessment (LD50 = 51 mg/kg) does not underestimate the potential hazard arising from 3-Acetylpyridine.

The second Klimisch 4 supporting study on rats revealed a LD50 = 46 µl/kg. Taking into account the test item’s density of 1.11, this value corresponds to 51 mg/kg, which is the same value as derived from the key study. Hence, the available values for the more relevant species for human risk assessment are consistent, and there are no indications given that the LD50 = 51 mg/kg is not relevant or may underestimate the hazard arising from 3-Acetylpyridine. So, no data gaps were identified, and no additional testing is required, the tonnage-driven data requirements under REACH are fully met.

LD50 = 51 mg/kg falls in the range of 50 < Category 3 ≤ 300 as indicated by Regulation (EC) No 1272/2008, and triggers the classification of the test item as acute toxic Cat. 3.

Justification for selection of acute toxicity – oral endpoint
Most reliable study (Klimisch 2 vs. 4), best documented, and closest to standard procedures and test animals.

Justification for classification or non-classification

The key value chosen for risk assessment is LD50 = 51 mg/kg, which falls in the range of 50 < Category 3 ≤ 300 as indicated by Regulation (EC) No 1272/2008, and triggers the classification of the test item as acute toxic Cat. 3.