Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 February - 13 April 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted by GLP accredited laboratory. Method according to OECD guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tropicate
- Substance type: pure active substance
- Physical state: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Six female Sprague-Dawley rats (SPF Caw) from Elevage JANVIER, France of 8-9 weeks old were selected having body weights from 205-215g.
A controlled environment was maintained in the room with optimal conditions of approximately 15/h air changes, a temperature of 19-25ºC, a relative humidity of 30-70% and a 12 hour light/12 hour dark cycle per day.
3 animals were present in a solid-bottomed polycarbonate cage with a stainless steel mesh lid containing sawdust bedding that was exchanged twice a day. Animals were acclimitised for a period of 5 days prior to exposure. The animals had free access to tap water and food (M20, SDS).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Animals were orally exposed to a single dose using syringe fitted with a oesophageal metal canula. The OECD guideline prescribes that the test substance should be administered in a single dose by gavage using a single dose. Therefore no vehicle was necessary.
Doses:
The dose level was 2000 mg/kg (2.06 ml/kg body weight) on day 0.
No. of animals per sex per dose:
3 female rates per group. Two groups of rats.
Control animals:
yes
Details on study design:
The animals were daily systematically examined on behavioural or toxic effects on the major physiological functions at 0.5, 1, 3, 4 and 24 hours after the administration of the test item and daily during the rest of the study period. Observations were compared to historical control data.
Animals were weighed on days 0 (just before administration), 2, 7 and 14.
On day 14, the animals were anaesthetised with sodium pentobarbital. Macroscopic observations were entered on individual autopsy sheets. Only those organs that were likely to be modified in case of acute toxicity were examined.
Statistics:
The method used is not intended to calculate a precise LD50, hence no statistical analysis was performed. The oral LD50 was ranked and an LD50 cut-off value determined based on the OECD 423 guideline.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
2 500 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: cut-off
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
One rat treated at 2000 mg/kg b.w. (1/6) died during the second step of the study at 24 hours and 45 minutes post-dose. The mortality was preceded by decrease or absence in spontaneous activity, in Preyer’s reflex, in muscle tone, mydriasis, piloerection, bradypnea, A decrease in body weight was also noted on the day of the death: -13% compared to day 0.
The macroscopical examinations of the dead animal revealed a thinning of the forestomach and a thickening of the corpus.
Clinical signs:
In the surviving animal treated at 2000 mg/kg b.w. (5/6), decrease in spontaneous activity (5/5) and in Preyer’s reflex (1/5), mydriasis (3/5), lacrymation (2/5) and piloerection (4/5) were noted. The animals recovered a normal behaviour at 24 hours post-dose.
Body weight:
The body weight evolution of the animals remained normal throughout the study (Table 1).
Gross pathology:
The macroscopical examinations of the surviving animals at the end of the study did not reveal treatment related change.

Any other information on results incl. tables

Table 1 Body weight and weight gain in grams of the six female rats subjected to the test substance at a dose of 2,000mg/kg bw.

  D0 D2 D2-D0 D7 D7-D0 D14 D14-D0
Females              
Rf 9658 214 217 3 230 16 248 34
Rf 9659 205 207 2 227 22 247 42
Rf 9660 208 216 8 230 22 246 38
Rf 9673 205 218 13 244 39 265 60
Rf 9674 215 220 5 247 32 264 49
Rf 9675 206 dead          
Mean 208.8 215.6 6.2 235.6 26.2 254.0 44.6
Std Dev 4.5 5 4.4 9.2 6.4 9.6 10.2

Dx (x=0,2,7,14) stands for the number of days after the administration of the test substance.

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information based Regulation EC No. 1272/2008. Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of the test substance in Wistar rats exceeds 2,000 mg/kg body weight. The LD50 cut-off value was considered s 2,500 mg/kg body weight by oral route in the rat.
Executive summary:

The acute toxicity class method (OECD 423 (2001)) was used to assess the acute toxicity of test substance in 6 female Sprague-Dawley rats.

The test substance was administered by oral gavage to the rats at a dose level of 2,000 mg/kg body weight. Animals were observed daily and their body weights were weekly recorded. Macroscopic examination was performed after sacrifice.

One mortality occurred on day 1. The other animals recovered normal behaviour within 24h.

The body weight gain was normal.

No abnormalities were found at post mortem macroscopical examinations of the animals.

The LD50 of the test substance exceeds 2,000 mg/kg body weight. Based on the result, the LD50 cut-off value is 2,500 mg/kg body weight.

Consequently, the test substance does not need to be classified according to Regulation EC No. 1272/2008.