2-Propyn-1-ol, reaction product with 1-2.5 moles of oxirane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: comparable to guideline study with acceptable restrictions. Source substance for RA information according to analogue justification.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction product of 2-Propyn-1-ol with methyloxirane

EC Number:

609-530-2

Cas Number:

38172-91-7

IUPAC Name:

Reaction product of 2-Propyn-1-ol with methyloxirane

Details on test material:

- Physical state: liquid
- Analytical purity: approx. 50%
- Impurities (identity and concentrations): < 1% Propargylalcohol, approx. 35% water, approx. 7% Propylenglycol, aprox. 7% higher alcoxylated products

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Weight at study initiation: male (mean): 186g, female (mean): 184g
- Fasting period before study: 16 hours
- Housing: 5 animals per cage (grouped according to doses)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): fully airconditioned
- Photoperiod (hrs dark / hrs light): 12 hours / 12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Doses:

215, 464, 2150, 5000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once per day (observation), after 7 and 13 days (weighing)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 464 - < 2 150 mg/kg bw

Based on:

test mat.

Remarks on result:

other: all male and female animals dosed with 2150mg/Kg died after 1 day, 2/5 males dosed with 464mg/Kg died after 7 days, 0/5 females dosed with 464mg/Kg died until the end of the study

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 464 - < 2 150 mg/kg bw

Based on:

test mat.

Remarks on result:

other: all female animals dosed with 2150mg/Kg died after 1 day; all female animals dosed with 464mg/Kg survived until the end of the study

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 464 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/5 male animals dosed with 464mg/Kg died 7 days after treatment

Mortality:

male/female:
5000mg/Kg: 5/5 animals after 1 day
2150mg/Kg: 5/5 animals after 1 day

male:
464mg/Kg: 2/5 animals after 7 days

No mortality was observed after administration of 215 mg/kg in males and females as well as after treatment of females with 464 mg/kg.

female:
5000mg/Kg: 5/5 animals after 1 day
2150mg/Kg: 5/5 animals after 1 day

Clinical signs:

other: 5000mg/Kg, males and females: dyspnea, apathy, abnormal position, atonia, paresis, poor general state after <15min - 4h staggering: <15min - 1h exsiccosis: 4h piloerection: 1h - 4h 2150mg/Kg, males and females: dyspnea, apathy, staggering, paresis, poor

Gross pathology:

male and female animals that died spontaneously on day 1 or 7:
general congestion, liver: lobular perphery yellow brown, stomach: bloody ulceration in the glandular stomach

sacrified animals (male, female): no pathological findings

Any other information on results incl. tables

LD50 male animals: ca. 464 mg/kg; LD50 female animals > 464 < 2150 mg/kg

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information GHS Criteria used for interpretation of results: EU

Executive summary:

ln principle, the methods described in OECD Guideline 401 were used without GLP compliance.

5 rats per sex and dose were treated simultaneously with concentrations of 5000, 2150, 464 and 215 mg/Kgby gavage with preparations of the test substance in water as vehicle.

Group-wise documentation of clinical signs was performed over a 14- day study period, where clinical signs and mortality were documented at least once daily. Mortality was observed among the high doses in both sexes after 24 hours: 5000 mg/kg (5/5) and 2150 mg/kg (5/5). At 465 mg/kg 2 of 5 male animals died.

On the basis of the observed lethality, the LD50 value was estimated to be > 464 <2150 mg/kg bw for female and about 464 mg/kg bw for male. As a conseqence of it, the test substance should be classified as acute oral toxicity category 4 (GHS). (BASF, 1987)