Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Five Wistar rats of each sex (females were nulliparous and non-pregnant).

Young adult animals (approx. 9 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.

Conditions:
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +/- 3.0 oC (actual range 19.6-22.7 oC), a relative humidity of 30-70% (actual range 27-64%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Accomodation:
Individually housed in labeled Macrolon cages (MIII type, height 15 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4; Technilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, BMI, Helmond, The Netherlands). Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Macrolon cages (MIV type).

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Single application at 2000 mg/kg body weight
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
five
Control animals:
no
Details on study design:
Observations:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales: Maximum grade 4 (grading slight (1) to very severe (4); Maximum grade 3 (grading slight (1) to severe (3); Maximum grade 1 (presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Chromodacryorrhoea, hunched posture and/or ptosis were noted in some animals on days 1 and/or 2. In one femaile, scabs were noted in the nect from day 9 onwards.
Body weight:
The changes noted in body weight gain in males and females were within the range expected fro rats used in this type of study and were therefore considered not indicative of toxicity.
Other findings:
In one animal the left testis was reduced in size

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of Pentamethyl-trioxepane in Wistar rats was established to exceed 2000 mg/kg body weight
Executive summary:

The dermal LD50 value of Pentamethyl-trioxepane in Wistar rats was established to exceed 2000 mg/kg body weight.

Data are conclusive but not sufficient for classification.