4-(hydroxymethyl)-4-methyl-1-phenylpyrazolidin-3-one

Endpoint summary

Description of key information

Five rats per sex received a single dose of 1100, 1500 or 2000 mg/kg bw by gavage. During the 14 day observation period 4, 6 and 9 animals died at 1100, 1500 and 2000 mg/kg respectively. These animals showed decreased body weight, apathy and letargy and effects on the antrum. Other animals survived and showed no clear treatment related effects (NOTOX 1985).

Based on these findings it is concluded that the LD50 is 1300 mg/kg bw (males and females combined).

In a limited report the LD50 is 556 mg/kg bw (Kodak 1992)

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:

22 February 1985 to 09 April 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

test according to OECD 401 under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

12 May 1981

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Central Institute for Breeding of Laboratory Animals TNO (CPB), Zeist, The Netherlands
- Females (if applicable) nulliparous and non-pregnant: no data
- Age at study initiation: no data
- Weight at study initiation: males 176-250 g; females 123-156 g
- Fasting period before study: yes (overnight until 2-4.5 hours after dosing)
- Housing: individually in macrolon cages
- Diet: standard pelleted lab feed (RMH, Hope Farms) ad libitum
- Water: tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 °C
- Humidity (%): 50-65%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE: propylene glycol

MAXIMUM DOSE VOLUME APPLIED: not indicated

DOSAGE PREPARATION (if unusual): sonicated for 3 hours (suspension)

Rationale for the selection of the doses: pre-test in 1 male/1 female per group at 13, 18, 24 and 32 mg/kg bw --> no deaths
additional pre-test in 1 male/1 female per group at 1300, 2400 and 3200 (male only) --> all dead within 4 days.

Doses:

1100, 1500 and 2000 mg/kg bw

No. of animals per sex per dose:

5 males + 5 females per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: once daily for mortality and clinical signs
- Frequency of weighing: on day 0, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

LD50 value according to Finney (1971)

Preliminary study:

pre-test in 1 male/1 female per group at 13, 18, 24 and 32 mg/kg bw --> no deaths
additional pre-test in 1 male/1 female per group at 1300, 2400 and 3200 (male only) --> all dead within 4 days.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 400 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 200 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 300 mg/kg bw

Based on:

test mat.

Mortality:

1100 mg/kg bw: 2 males and 2 females (before day 6)
1500 mg/kg bw: 2 males and 4 females (before day 6)
2000 mg/kg bw: 4 males and 5 females (before day 6)

Clinical signs:

other: apathy and lethargy during the initial days

Gross pathology:

in animals that died: diminution of antrum (sometimes with enlarged forestoach and petechiae in 5 animals; no abnormalities in others
in survivors: yellow granules in the stomach (2 animals); whitish material in the bladder (3 animals); no abnormalities in others

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 is 1300 mg/kg bw

Executive summary:

Five rats per sex received a single dose of 1100, 1500 or 2000 mg/kg bw by gavage. During the 14 day observation period 4, 6 and 9 animals died at 1100, 1500 and 2000 mg/kg respectively. These animals showed decreased body weight, apathy and letargy and effects on the antrum. Other animals survived and showed no clear treatment related effects.

Based on these findings it is concluded that the LD50 is 1300 mg/kg bw (males and females combined).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 300 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the findings in the test the substance needs to be classified as harmful if swallowed (H302) according to EC 1272/2008 (CLP)