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Administrative data

Endpoint:
chronic toxicity: dermal
Type of information:
other: published data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
SIAM 22
Author:
OECD SIDS
Year:
2006
Bibliographic source:
TOME 2: SIDS Dossiers
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Decan-1-ol
EC Number:
203-956-9
EC Name:
Decan-1-ol
Cas Number:
112-30-1
IUPAC Name:
decan-1-ol
Details on test material:
Fatty alcohol blend (56.7% 1-decanol CAS № 112-30-1, 42.7% octanol CAS № 111-87-5):

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- 10 of each gender per test group and control group

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: 0.9% Sodium chloride (this was dosed to the control group at a dose volume of 1.2 ml/kg.
Details on exposure:
TEST SITE
- Area of exposure: dorsal skin

- Type of wrap if used: gauze binder, secured with tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test article was removed from the application site with a wet paper towel

- Time after start of exposure: six hours

TEST MATERIAL - Control group
- Amount(s) applied (volume or weight with unit): 1.2 ml/kg

- Concentration (if solution): 0.9% saline

- Constant volume or concentration used: yes
TEST MATERIAL - Test groups(1-3)
- Amount(s) applied (volume or weight with unit): 100, 300 and 1000 mg/kg/day respectively
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
The application sites were wrapped for six hours with a gauze binder, secured with tape.
Frequency of treatment:
Application for five days a week over thirteen consecutive weeks to the shaved intact dorsal skin of each rat for a minimum of 65 applications.
Doses / concentrations
Remarks:
Doses / Concentrations:
100, 300 and 1000 mg/kg/day
Basis:
other: volume or weight with unit
No. of animals per sex per dose:
Control group: 20 rats (10 male and 10 female) which received 0.9% saline on a comparable regimen at a dose volume of 1.2 ml/kg.

Three test groups: 20 rats (10 males and 10 females) administered dosage levels of 100, 300 and 1000 mg/kg/day respectively.
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
The animals were observed for signs of overt toxicity, dermal irritation, effects on body weight and consumption, haematology and serum chemistry parameters.
Sacrifice and pathology:
Complete necropsies were performed on all animals.
Other examinations:
Selected organs were weighed and a microscopic examination was conducted on selected tissues from all animals at the scheduled necropsy.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Marked dermal irritation was noted in all dose groups and consisted of very slight to severe erythema, very slight to moderate edema, persistant desquamation, eschar, exfoliation, clear exudate and fissuring.
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
Marked dermal irritation was noted in all dose groups and consisted of very slight to severe erythema, very slight to moderate edema, persistant desquamation, eschar, exfoliation, clear exudate and fissuring.
Mortality:
mortality observed, treatment-related
Description (incidence):
Marked dermal irritation was noted in all dose groups and consisted of very slight to severe erythema, very slight to moderate edema, persistant desquamation, eschar, exfoliation, clear exudate and fissuring.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
The mean body weights were lower in the middle and high dose groups compared to the control group. This was attributed to the test article.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Mean food consumption (evaluated as g/animal/day) was slightly but consistently decreased in the high dose group (males) during the first two thirds of the study period, and this was attributed to the test article.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Description (incidence and severity):
No information provided
Ophthalmological findings:
not specified
Description (incidence and severity):
No test related ophthalmic lesions were present at the week 12 opthalmologic examinations.
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Mean white blood cell counts were increased in a non dose related manner in all the test groups (not the control). This was attributed to the acute dermal inflammation that was observed.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
In the serum chemistry parameters albumin means were decreased and globulin means were increased (resulting in decreased A/G ratios). Again this was attributed to the acute dermal inflammation that was observed.
Urinalysis findings:
not specified
Description (incidence and severity):
No information provided
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
The adrenals, brain, kidneys, liver, ovaries and testes were weighed at necropsy. No remarkable statistically significant changes in organ weight were note for any of the organs, except for the adrenals.
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No significant changes reported (except for the dermal application sites for all the dose groups)
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
No significant changes reported (except for the dermal application sites for all the dose groups)

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: on the basis of a lack of systemic effects reported in the study, the NOAEL following dermal administration of fatty alcohol blend for a minimum of 90 days is greater than 1000 mg/kg/day.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Clinical signs

Vocalisation (due to pain) was the predominant sign observed in the high dose group (females) generally on one to three days most often during the second week of test article administration. Excessive struggling was also reported during exposure on single occasions for one male in the low dose group and two female in the high dose group. Hypersensitivity to touch was also reported on two separate occasions for a single high dose male.

                                                                                                          

Marked dermal irritation was noted in all dose groups and consisted of very slight to severe erythema, very slight to moderate edema, persistant desquamation, eschar, exfoliation, clear exudate and fissuring.

Organ weights

The adrenals, brain, kidneys, liver, ovaries and testes were weighed at necropsy. No remarkable statistically significant changes in organ weight were note for any of the organs, except for the adrenals which was most likely related to stress resulting from severe dermal irritation that was observed in all dose groups.

Macroscopic examination

The only test article related gross lesions observed included scabbing and thickening of the skin at the test site. (Irritant related effects). There were no other test article related gross findings at the scheduled necropsy.

Applicant's summary and conclusion

Conclusions:
Based on the data that was reported a NOAEL following dermal administration of fatty alcohol blend for a minimum of 90 days was less than 100 mg/kg/day.
However the NOAEL has been based on a local irritation effect rather than a systemic effect. Therefore it is proposed (by the author of the EPSR) that on the basis of a lack of systemic effects reported in the study, the NOAEL following dermal administration of fatty alcohol blend for a minimum of 90 days is greater than 1000 mg/kg/day.
Executive summary:

 A 90-day dermal toxicity study in rats with fatty alcohol blend (56.7% decanol, 42.7% octanol) at dose levels of 0, 100, 300, or 1,000 mg/kg resulted in severe irritation at the application site. Severe irritation including fissuring of the skin occurred in 40% of the animals at 100 mg/kg/day and 80% of the animals at the limit dose. Slight changes in hematology, clinical chemistry, and organ weights were noted at the limit dose of 1,000 mg/kg/day.