Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 24, 2008 to August 28, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
Adopted December 17, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
Purity: 99%
Specific Gravity: 1.49

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: ~8-9 weeks
- Weight at study initiation: 196-212 grams
- Fasting period before study: 16-20 hours prior to dosing
- Housing: 1/cage
- Diet: ad libitum, except for 16-20 hours prior to dosing
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: June 25, 2008 To: July 10, 2008

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 0.26-0.28 mL
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed 0.5, 1, 2, and 4 hours postdose and once daily for 14days for toxicity and pharmacological effects. All animals were observed twice daily for mortality. Body weights were recorded immediately pretest, weekly and at termination.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not applicable

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality reported
Mortality:
All animals survided the 2000 mg/kg oral dose
Clinical signs:
Instances of wetness of the anogenital area, ataxia, prostration, flaccid muscle tone and coma were noted on the day of dosing. All animals appeared normal from day 1 through day 14.
Body weight:
body weight changes were normal in 4/5 animals. One animal lost weight during the second week of the observation period.
Gross pathology:
Necropsy results were normal.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
All animals survived the 2000 mg/kg oral dose with transient clinical signs observed during the day of dosing. The symptoms occurred quickly after dosing and were transient in nature. The acute oral LD50 is greater than 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the substance was investigated following a GLP compliant OECD Guideline 425 study. In total, five female non-pregnant and nulliparous Wistar albino rats were dosed with 2000 mg/kg bw of OFPMA according to up-and-down procedure. The rats were observed at 0.5, 1, 2, and 4 hours post dose and once daily for 14 days for toxicity and pharmacological effects. All animals were observed twice daily for mortality. Body weights were recorded immediately pretest, weekly and at termination. All animals were examined for gross pathology.

 

All animals survived the 2000 mg/kg bw oral dose with transient clinical signs observed during the day of dosing. Instances of wetness of the anogenital area, ataxia, prostration, flaccid muscle tone and coma were noted on the day of dosing. The symptoms occurred quickly after dosing and were transient in nature. All animals appeared normal from day 1 through day 14. Body weight changes were normal in 4/5 animals. One animal lost weight during the second week of the observation period. Necropsy results were normal.

 

The acute oral LD50 of the substance is greater than 2000 mg/kg bw.