Registration Dossier

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: Meets generally accepted scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar 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:
- Name of test material (as cited in study report): D-Pantolacton kristallin
- Physical state: solid white crystals
- Analytical purity: >99 %

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
- Age at study initiation: young adults
- Weight at study initiation: males: approx. 183 g; females: approx. 173 g
- Fasting period before study: about 16 h before administration
- Housing: in stainless steel wire mesh cages, type DK-III (Becker & Co. Castrop-Rauxel, Gemany)
- Diet: Kliba Labordiaet 343 (Klingentalmuehle AG, Kaiseraugst, Switzerland); ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 20-24 °C
- Humidity: 30-70 %
- Air changes per hr: the animals were housed in fully air-conditioned rooms
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses:
464, 1000 and 2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
Signs and symptoms:
- Time of day of administration: in the morning
- Observation period: 14 days
- Signs and symptoms: recording of signs and symptoms several times on the day of administration, at least once each workday. Check for moribund and dead animals twice each workday and once on holidays.

Pathology:
Withdrawal of food about 16 h before sacrifice with CO2; then necropsy with gross-pathological examination. Necropsy of all animals that died as early as possible.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
In the 2000 mg/kg bw dose group, 3/5 female animals died within the first hour after administration of the test material. All animals of the other dose groups (males and females) survived until the end of the study period.
Clinical signs:
No clinical signs of toxicity were observed in all animals of both sexes dosed with 464 or 1000 mg/kg bw of the test material.
The following clinical signs of toxicity were observed in the male animals of the 2000 mg/kg bw group: poor general state (H0-D1), dyspnoea (H0-D1), apathy (H0-D1), staggering (H0-H4), twitching (H0-H1), spastic gait (H0-H1).
The following clinical signs of toxicity were observed in the surviving female animals of the 2000 mg/kg bw group: poor general state (H0-H4), dyspnea (H0-H4), apathy (H0-H4), lateral position (H0), tremor (H0), twitching (H0), saltatory spasm (H0), flexion spasm (H0), tonic convulsions (H0), clonic convulsions (H0), salivation (H0), chromodacryorrhea (H0).
(H = hour; D = day)
Body weight:
Body weight gain was within the normal range. For details see "Remarks on results including tables and figures".
Gross pathology:
- Animals that died during the study (3 females at 2000 mg/kg bw): general congestion.
- Sacrificed animals (males and females): no pathological findings noted.

Any other information on results incl. tables

Table 1: Mean body weights of the animals during the study period:

sex

time point

mean body weight (g) for dose group 464 mg/kg bw

mean body weight (g) for dose group 1000 mg/kg bw

mean body weight (g) for dose group 2000 mg/kg bw

male

before application

180

188

180

after 7 days

254

259

 

after 8 days

 

 

260

after 10 days

 

 

274

after 13 days

289

293

female

before application

178

169

  171

after 7 days

209

203

 

after 8 days

 

 

204

after 10 days

 

 

208

after 13 days

220

216

 

Applicant's summary and conclusion