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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 04 - September 12, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 22.03.1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
Granulated textured wood (Granulate A2, J. Brandenburg, D-49424 Goldenstedt) was used as bedding material for the cages. The cages were changed and cleaned twice a week.
Penodic analysis of the bedding material for contaminants based on EPA/USA IS conducted at least once a year by LUFA-ITL 4 (see Appendix 1: Limitation for contaminants in the bedding material).
During the 14-day observation penod the animals were kept in groups of 2 - 3 animals in MAKROLON cages (type Ill) at a room temperature of 22°C ± 3°C (maximum range) and a relative humidity of 55% ± 15% (maximum range). Deviations from the maximum range caused for example during cleaning procedures are dealt with in SOPs.
The rooms were lit (about 150 lux at approx. 1.50 m room height) and darkened for periods of 12 hours each.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
the test substance was used as supplied for the 2000 mg/kg dose; corn oil was used as vehicle for the 200 mg/kg dose and for the 25 mg/kg dose
Doses:
step 1: 2000 mg/kg b.w.
step 2: 200 mg/kg b.w.
step 3: 25 mg/kg b.w.
No. of animals per sex per dose:
three animals per step
Control animals:
no
Details on study design:
Observations were performed before and immediately, at 5, 15, 30 and 60 min, as well as at 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days.
During the follow-up period (at least 2 weeks), changes of skrn and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system, somatomotor activity as well as behav1our pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to poss1ble tremor, convulsions, salivation, diarrhoea, lethargy, sleep and
coma. Observations on mortality were made at least once daily with appropriate actions taken to minimize loss of animals during the study. The time of death is recorded as precisely as possible. Individual body weights were recorded before administration of the substance and thereafter in weekly rntervals up to the end of the study, and at death. Changes in weight were calculated and recorded. At the end of the experiments (in the morning of test day 15), all survivrng animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. From animals which survived 24 hours or longer, a microscopic examination of all organs which showed evident lesions was performed.
Autopsy and macroscopic inspections of animals which died prematurely would have been carried out as soon as possible after exitus.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 50 - < 200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: based on interpretation scheme OECD 423, 22.03.1996
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 25 - < 200 mg/kg bw
Based on:
test mat.
Mortality:
Step 1: male, 2000 mg/kg bw; number of animals: 3, number of deaths: 3
Step 2: male, 200 mg/kg bw; number of animals: 3, number of deaths: 1
Step 3: female, 200 mg/kg bw; number of animals:3, number of deaths: 2
Step 4: male, 25 mg/kg bw; number of animals:3, number of deaths: 0
Step 5: female, 25 mg/kg bw; number of animals:3, number of deaths: 1
Clinical signs:
at 2000 mg/kg b.w.: reduced motility, atax1a, reduced muscle tone, dyspnoea and mydriasis
at 200 mg/kg b.w.: reduced motility, ataxia, reduced muscle tone and dyspnoea.
at 25 mg/kg b.w.: No signs of systemic toxicity were noted
Body weight:
All surviving an1mals gamed the expected body weight within the study period
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The oral LD50 value for PNCl2 in CD® rats was ranked within the LD50 range of > 50 - 200 mg/kg body weight.
Executive summary:

The acute toxic class method according to OECD Guideline No. 423 was performed with the test item.

PNCI2 was administered orally by gavage to three male CD® rats at 2000 mg/kg body weight/ to six CD® rats (3 /sex) at 200 mg/kg body weight and in addition, to six CD® rats (3 / sex) at 25 mg/kg body weight. Animals were subjected to daily observations and weekly determinations of body weight. Macroscopic exammation was performed immediately after premature death or after terminal sacrifice (test day15).

2000 mg/kg b.w. resulted in the death of all male CD® rats within 60 minutes. The following symptoms were noted at 2000 mg/kg b.w.: reduced motility/ ataxia, reduced muscle tone, dyspnoea and mydriasis.

200 mgl/g b.w. resulted in the death of one male within 60 minutes and of two female CD® rats within 8 days. The following symptoms were noted at 200 mg/kg b.w.: reduced motility/ ataxia/ reduced muscle tone and dyspnoea.

25 mg/kg b.w. resulted in the death of one female CD® rat within 5 days. No signs of systemic toxicity were noted at 25 mg/kg b.w.

All surviving animals gamed the expected body weight within the study penod. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value for PNCI2 in CD® rats was ranked within the LD50 range of 25 - 200 mg/kg body weight. According to the interpretation scheme of OECD 423 adapted 22.03.1996 the LD50 ranges between > 50 - < 200 mg/kg body weight.