Poly(oxy-1,2-ethanediyl), .alpha.,.alpha.'-2-butyne-1,4-diylbis[.omega.-hydroxy-

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:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1972

Report date:

1972

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(no data on test substance purity, reduced observation period, limited documentation)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxyethylated 2-butyne-1,4-diol

EC Number:

608-711-3

Cas Number:

32167-31-0

Molecular formula:

C4 H6 O2 (C2 H4 O) n, where 1 < n < 4.5

IUPAC Name:

Hydroxyethylated 2-butyne-1,4-diol

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Golpanol BEO = Golpanol SC 9189
- Physical state: liquid
- Analytical purity: no data

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gassner, Germany
- Mean body weight at study initiation: males 267 g, females 187 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 16% (G/V)

MAXIMUM DOSE VOLUME APPLIED: 15.6 mL/kg bw

Doses:

640, 800, 1000, 1250, 1600, 2000 and 2500 µL/kg bw (corresponding to approx. 730, 912, 1136, 1423, 1824, 2280, 2859 mg/kg bw; calculation based on density of 1.14 g/cm³)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Body weight was determined before the beginning of the study for dose calculation.
Observation of clinical signs was several times on the day of administration and once daily afterwards with the exception of weekends and holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

N/A

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 824 mg/kg bw

Based on:

test mat.

Mortality:

730 and 912 mg/kg bw: no deaths occured;
1136 mg/kg bw: 1/10 animals (males: 1/5 animals died 7 days after treatment; females: 0/5 animals died).
1423 mg/kg bw: 1/10 animals (males: 1/5 animals died within 48 hours after treatment; females: 0/5 animals died).
1824 mg/kg bw: 5/10 animals (males: 1/5 animals died within 48 hours after treatment, 3/5 animals were dead at the end of the observation period of 7 days; females: 1/5 animals died within 48 hours after treatment, 2/5 animals were dead at the end of the observation period of 7 days).
2280 mg/kg bw: 5/10 animals (males: 3/5 animals died within 48 hours after treatment, 4/5 animals were dead at the end of the observation period of 7 days; females: 1/5 animals died within 48 hours after treatment, 1/5 animals were dead at the end of the observation period of 7 days).
2859 mg/kg bw: 10/10 animals (males: 2/5 animals died within 24 hours after treatment, 5/5 animals died within 48 hours after treatment; females: 2/5 animals died within 24 hours after treatment, 5/5 animals died within 48 hours after treatment).

Clinical signs:

other: On the first study day accelerated respiration, crouched position, reddened, partly closed eyes. On the following observation days crouched position, partly abdominal position, intermittent breathing and reddened eyes. After the 5th day no symptoms.

Gross pathology:

Perished animals: 1136, 1423, 1824, 2280 mg/kg bw: kidney and liver: acute congestive hyperemia; dilatation of the heart; thymic petechiae; slight lung edema; liver: loam-yellow-grey with peripheral lobular pattern (peripheral fatty degeneration, necroses).
Sacrificed animals: no abnormalities were noted at necropsy of animals sacrificed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Executive summary:

The non-GLP acute oral toxicity study was performed according to a standardized BASF test protocol. In principle this test protocol is similar to the the OECD Guideline 401: Wistar rats (5/sex/dose) were administered a single oral dose (gavage) of the test item (analytical purity: unknown) at dose levels of 640, 800, 1000, 1250, 1600, 2000 and 2500 mg/kg body weight (bw). The test item was applied as aquaeous solution at a concentration of 16% w/v and at a maximum dose volume of 15.6 mL/kg bw.

The animals were observed for a post-dosing period of 7 days. Subsequently, all surviving animals were killed and like animals that died during the study subjected to gross pathology.

Mortality occurred in the high dose group within 24 hours after application of the test item and symptoms reported were described as accelerated respiration, crouched position, reddened, partly closed eyes. On following observation days crouched position, partly abdominal position, intermittent breathing and reddened eyes were observed. From the 6th day of observation animals were without findings.

No data were available on body weight gain. Gross necropsy findings in rats that died included acute congestive hyperemia, dilatation of the heart, thymic petechiae, slight lung edema, loam-yellow-grey liver with peripheral lobular pattern. No abnormalities were noted at necropsy of animals sacrificed at the end of the study.

The acute oral toxicity study is acceptable (reliability 2), though not fully compliant with the actual guideline requirements for an oral toxicity test (OECD 401) in rats (incomplete characterisation of the test substance - purity not given in the study report, observation period shortened - 7 instead of 14 days).

Under the conditions of the study the LD50 of the test item after oral application was determind to be 1824 mg/kg bw.

 

 

Classification of the test item for acute oral toxicity as Xn, R22 according EU Directive 67/548/EC as well as Cat 4, H302, Harmful if swallowed according to the CLP Regulation 1272/2008 is warranted.