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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Dec 23, 2008 - May 07, 2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: For this endpoint supporting data for a main most critical degradation product are provided. The relevant study was performed according to GLP and the methods applied are fully compliant with OECD TG 423.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Manston Road. Margate, Kent, UK
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 163-191 g
- Fasting period before study: overnight before dosing
- Housing: groups of3 in polypropylene cages
- Diet (e.g. ad libitum):ad libitum, except for a period of overnight food deprivation before dosing
- Water (e.g. ad libitum): ad libitum, except for a period of overnight food deprivation before dosing
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21 °C
- Humidity (%): 36 - 61 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: day 1 To: day 15

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: test item was soluble in water
- Lot/batch no. (if required): --
- Purity: --

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual):
Formulations were prepared on the day of dosing. The appropriate amount of
N·butylpyridinium chloride was weighed and the requisite weighed amount of water was
added. Mixing was by magnetic stirring until the formulation was visibly homogeneous. The
formulation at 200 mglmL was prepared volumetrical ly, that is, the amount of
N·butylpyridinium chloride was weighed and water was added to the graduated mark.
The pH of the formulation at 30 mglmL was pH 6 and at 200 mg/mL was pH 5.36.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
The potential oral toxicity of the test item was nOl known before the start of the study.
Therefore the Study Director selected 300 mg/kg as a suitable starting dosage for
administration to a group of 3 females.
Doses:
300, 2000 mg/kg bw
No. of animals per sex per dose:
3 per dose group (total 9)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days 1, 8, 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
No formal stati stical analysis was conducted.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals that received 2000 mglkg were euthanised 5 h after dosing on the day of dosing (Day 1) due to the severity of their signs. There were no unscheduled deaths among the 6 animals that received 300 mg/kg.
Clinical signs:
At 300 mg/kg, there were no adverse signs of reaction to treatment recorded in any animal.
At 2000 mglkg, the animals began to di splay hunched appearance, a red nasal discharge, staggering gait and subdued behavior from 3 1/4 h after dosing and at 5 h all of these rats were affected by each of these signs. In addition, the breathing of one animal was laboured at the 4 1/2 and 5 h observation.
Body weight:
Body weight gains of surviving animals were considered to be acceptable for rats of this age and strain.
Gross pathology:
Macroscopic findings were only recorded in the 3 decedent animals that received 2000 mglkg. These animals all displayed darkening to all lobes of the liver and in one animal all Liver lobes were prominent.
The spleen of one animal was pale. Both uterine horns of one animal were dilated with fluid to a diameter of 4 mm and the intestines from another animal were prominent and had abnormal (liquid) contents. These findings are considered to be background findings that are occasionally seen in studies of this type at these laboratories.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The median lethal oral dose was considered to be between 300 and 2000 mg/kg bw.
Executive summary:

Study Design

This study investigated the acute oral toxicity of the test item, N-butylpyridinium chloride, after a single adminislration to Sprague-Dawley rats.
N-butylpyridiniurn chloride was administered to 2 groups of 3 females at 300 mg/kg and to one group of 3 females at 2000 mglkg. The vehicle was water and the dose volume was 10 mL/kg. Animals were observed for adverse signs of reaction to treatment up to 14 days after dosing. Body weights were recorded weekly and all animals were subjected to a gross necropsy.
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 423.

Results

All 3 animals that received 2000 mg/kg were euthanised 5 h after dosing on the day of dosing (Day 1) due to the severity of their signs. These animals began to display hunched appearance, a red nasal discharge, staggering gait and subdued behaviour from 3h after dosing and at 5 h all of these rats were affected by each of these signs. In addition, the breathing of one animal was laboured at the 4  h and 5 h observation.
Macroscopic fmdings recorded at necropsy included darkening to all lobes of the liver and all liver lobes of one animal were also prominent. The spleen of a second decedent was pale. There were no unscheduled deaths among the 6 animals that received 300 mg/kg and no adverse signs of reaction to treatment were recorded. Body weight gains were considered to be acceptable for rats of this age and strain and there were no macroscopic abnormalities at necropsy on Day 15.

Conclusion

Under the conditions of the study, after a single oral administration of N-butylpyridinium chloride to Sprague-Dawley rats at dosages of 300 mg/kg and 2000 mg/kg, all 3 animals that received 2000 mg/kg were humanely killed because of the severity of their clinical signs. There were findings of darkened lobes in the liver of the animals that received 2000 mg/kg. There was no evidence of toxicity at 300 mglkg. Therefore, the median lethal oral dose was considered to be between 300 and 2000 mg/kg bw.