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

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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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

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:
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 of observation animals were without findings.
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

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.