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Toxicological information

Acute Toxicity: oral

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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:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
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
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
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:
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 general state: 15min - 4h
abnormal position: 30min - 4h
atonia: 4h
pilolerection: 4h (only females)

464mg/Kg, males and females:
dyspnea, apathy, poor general state: 3 days,
staggering: 3 days (only males)
Body weight:
The rats were weighed on day 7 and 13 after treatment. None of the animals dosed with 5000 or 2150mg/Kg survived until these time points.

mean weights of males/females in dose group 464mg/Kg:
at beginning of the test: 178/180
after 7 days: 233/209
after 13 days: 276/220

mean weights of males/females in dose group 215mg/Kg:
at beginning of the test: 190/179
after 7 days: 260/210
after 13 days: 288/218
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)