Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.3200 (Repeated Dose Dermal Toxicity -21/28 Days)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.9 (Repeated Dose (28 Days) Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
other: MAFF Japan Agricultural Chemicals Regulation Laws 2-1-10 Notification 12 Nousan 8147 (2000)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Purity: 99.4%
Impurities: Not reported

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Details on species / strain selection:
The Crl:CD(SD) rat was selected based on consistently acceptable health status and on extensive experience with the strain at test facility.
Sex:
male/female

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
Deionized
Duration of treatment / exposure:
29 days
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
350 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Ophthalmological findings:
effects observed, non-treatment-related
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, non-treatment-related
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
other: Based on the lack of test substance-related effects on any in-life, clinical pathology, or anatomic pathology parameters in rats treated dermally up to 1000 mg/kg/day.
Sex:
male/female

Applicant's summary and conclusion

Conclusions:
NOAEL (males/females): 1000 mg/kg bw/d (Highest concentration tested) (based on the lack of test substance-related effects on any in-life, clinical pathology, or anatomic pathology parameters)
Executive summary:

The study was conducted according to guidelines, U.S. EPA OPPTS 870.3200 and OECD Guideline 410 to assess the potential repeated-dose dermal toxicity of test substance in rats. Four groups of young adult male and female rats (10/sex/group) were administered the test substance dermally for approximately 6 hours/day at dosages of 0, 100, 350, or 1000 mg/kg body weight (bw)/day for 29 days. Body weights, food consumption, and detailed clinical observations were evaluated weekly. The animals were evaluated for acute signs of systemic toxicity on days detailed clinical observations were not conducted. Ophthalmological evaluations were performed prior to the start of dermal exposure and near the end of the exposure period. Clinical pathology endpoints (hematology, coagulation, clinical chemistry, and urinalysis) were evaluated at the end of the exposure period. On test Day 29, the rats were sacrificed and given a gross and microscopic pathological evaluation.

No deaths occurred and no clinical or ophthalmological observations were attributed to exposure of the test substance. No adverse or test substance-related effects on body weight or nutritional parameters were observed.

There were no test substance-related effects on clinical pathology parameters, organ weights, gross pathology, or microscopic pathology.

The no-observed-adverse-effect level (NOAEL) for male and female rats was 1000 mg/kg bw/day. The NOAEL was based on the lack of test substance-related effects on any in-life, clinical pathology, or anatomic pathology parameters in rats treated dermally up to 1000 mg/kg/day.