3-(methylthio)propionaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985-08-20 to 1985-11-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 12 May 1981

Deviations:

yes

Remarks:

no information on analytical purity

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: FIFRA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals; Office of Pesticide Programs, U.S. Environmental Protection Agency, Office of Pesticides and Toxic Substances, November 1982; Section 81-1, Acute Oral Tox

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: TSCA: Health Effects Test Guidelines, Office of Toxic Substances, Office of Pesticides and Toxic Substances, United States Environmental Protection Agency, August 1982 Acute Exposure, Oral Toxicity

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(methylthio)propionaldehyde

EC Number:

221-882-5

EC Name:

3-(methylthio)propionaldehyde

Cas Number:

3268-49-3

Molecular formula:

C4H8OS

IUPAC Name:

3-(methylthio)propionaldehyde

Test animals

Species:

rat

Strain:

other: CDR (Sprague-Dawley derived) Albino Rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals
- Source: Charles River Breeding Laboratories, Inc., Wilmington, USA
- Age at study initiation: approx. 9 - 12 wks old; females were nulliparous and non-pregnant
- Weight at study initiation: 231 - 318 g (males) and 215 - 227 g (females)
- Acclimation period: 8, 15 or 16 days
- Fasting over-night (approx. 18 h) prior to treatment
- Housing: Grouped housing (six/cage) during equilibration. Individually housed during study.
- Diet: Purina Laboratory Chow, 5001; ad libitum
- Water: Municipal water; ad libitum

Environmental conditions
- Temperature (°C): 19 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DOSAGE PREPARATION: The test material was administered as received, no preparation was necessary. Animals received the same concentration of the undiluted test substance. Body burdens were adjusted via the applied volume.

Doses:

Males: 250, 350, 500, 600 and 700 mg/kg bw
Females: 700, 850, 1000, 1200 and 1700 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: approximately 1, 2 and 4 h after dosing and daily thereafter
- Frequency of weighing: pre-fasting, post-fasting (weights used for calculation of doses), Day 7 and Day 14
- Necropsy of survivors performed: Yes, all animals surviving at termination of the post exposure observation period were sacrificed and examined grossly. All abnormalities were recorded but no tissues were saved.
- Other examinations performed: Yes, food consumption was observed in the 14-days observation period.

Statistics:

- The LD50 was estimated with 95% confidence limits by calculation according to Miller, Lloyd C. & Tainter, M.L.
- Source: Estimation of the ED50 and its errors by means of logarithmic-probit graph paper; Proc. Soc. Exp. Bio. Med 57: 261-264 (1944)

Results and discussion

Preliminary study:

A range-finding experiment was conducted with one male and one female rat per dose.
- The doses tested were 350, 500, 700, 1000, and 1500 mg/kg bw.
- The post exposure observation time was 7 days.
- One male animal died after exposure to >= 700 mg/kg bw.
- The female rats died at doses of 1000 and 1500 mg/kg bw.

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

490 mg/kg bw

Based on:

test mat.

95% CL:

>= 402 - <= 578

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 050 mg/kg bw

Based on:

test mat.

95% CL:

>= 854 - <= 1 246

Mortality:

250 mg/kg bw (males only): No mortality occurred.
350 mg/kg bw (males only): No mortality occurred.
500 mg/kg bw (males only): 4/5 males died (1 h - 2 days post-dose).
600 mg/kg bw (males only): 2/5 males died (2 h post-dose).
700 mg/kg bw: 5/5 males and 1/5 females died (2 - 4 h post-dose).
850 mg/kg bw (females only): 1/5 females died (2 h post-dose).
1000 mg/kg bw (females only): 2/5 females died (2 h post-dose).
1200 mg/kg bw (females only): 5/5 females died (1 - 4 h post-dose).
1700 mg/kg bw (females only): 4/5 females died (1 - 24 h post-dose).

Clinical signs:

≥ 250 mg/kg bw: oral, ocular and nasal discharge, hypopnea, dyspnoea, urinary staining or hypoactivity after dosing in males and females and decreased food consumption on study Days 1 and 2, effects reversible in surviving animals by study Day 3.
≥ 500 mg/kg bw: ataxia, dry and wet rales, prostration, eyes partially closed, ocular discharge after dosing in males and females and decreased food consumption up to study Day 4, effects reversible in surviving animals by study Days 4 - 5.

Body weight:

The majority of surviving animals had gained weight both 7 and 14 days after dosing.
1700 mg/kg bw: Body weight loss at Day 7 in the single surviving female.

Gross pathology:

250 and 350 mg/kg bw: No abnormal findings.
500 mg/kg bw: discoloration of lungs in 3/4 dead males, testes in body cavity of 2/4 dead males, red walls of stomach in 1/4 dead males, red walls + red fluid in intestine in 4/4 dead males.
600 mg/kg bw: discoloration of lungs in 2/2 dead males, testes in body cavity of 1/2 dead males, red walls + red fluid in intestine in 2/2 dead males.
700 mg/kg bw: discoloration of lungs in 5/5 dead males, testes in body cavity of 1/5 dead males, red walls of stomach in 1/5 dead males, test material in stomach in 2/5 dead males, red walls + red fluid in intestine in 5/5 dead males; uterus reddened in 1/4 and uterus swollen in 1/4 surv. females.
850 mg/kg bw: discoloration of lungs in 1/1 dead females, reddened ovaries in 2/4 surv. females, uterus reddened in 2/4 surv. females, red walls + fluids of the intestine in 1/1 dead females.
1000 mg/kg bw: discoloration of lungs in 2/2 dead females, reddened uterus in 1/3 surv. females, swollen uterus in 1/3 surv. females, red walls of stomach in 1/2 dead females, red walls + fluids of the intestine in 2/2 dead females.
1200 mg/kg bw: red foci in lungs of 2/5 dead females, discoloration of lungs in 5/5 dead females, swollen uterus in 2/5 dead females, red walls and wrinkled stomach each in 1/5 dead females, test material content in the stomach of 4/5 dead females, white precipitate in the stomach of 3/5 dead females, red walls of the intestine in 1/5 dead females, contents of test material in the intestine in 2/5 dead females.
1700 mg/kg bw: post-mortem internal autolytic changes in 1/4 dead females, red foci of lungs in 1/4 dead females, discoloration of lungs in 4/4 dead females, swollen uterus in 1/4 dead females, red walls of stomach in 2/4 dead females, contents of test material in the stomach of 4/4 dead females, white precipitate in the stomach of 3/4 dead females, red fluid of the intestine in 2/4 dead females, contents of test material in the intestine in 1/4 dead females.

Other findings:

Food consumption:
Most animals had decreased food consumption beginning on the day after dosing. Food consumption recovered back to normal by study Day 5 onwards.

Any other information on results incl. tables

- Changes in surviving animals sacrificed after 14 days were compared in the study report to those of control animals. However, no other reference is made to control animals in this study.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 for male rats was determined to be 490 mg/kg bw and that of female rats to be 1050 mg/kg bw.
CLP: Acute Oral 4 (H302) according to Regulation (EC) No. 1272/2008